跳到主要內容

臺灣博碩士論文加值系統

(44.192.92.49) 您好!臺灣時間:2023/06/08 07:09
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:唐丕蓓
研究生(外文):Pi-Pei Tang
論文名稱:p53誘發IW32血癌細胞死亡與分化機轉的探討
論文名稱(外文):Studies of the Mechanisms Underlying p53-Induced Apoptosis and Differentiation in IW32 Erythroleukemia Cells
指導教授:陳芬芳陳芬芳引用關係
指導教授(外文):Fung-Fang Wang
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:150
中文關鍵詞:分化酪氨酸磷酸水解脢血癌細胞細胞凋亡p53
外文關鍵詞:p53differentiationapotosisErythroleukemia cellprotein tyrosine phosphatase
相關次數:
  • 被引用被引用:0
  • 點閱點閱:246
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
抑癌蛋白p53為一轉錄因子,參與調控細胞生長、DNA修補、分化與死亡,其生物功能主要為保護基因體防止細胞癌化。 吾人以IW32紅血球血癌細胞為模式,探討p53的作用機制。 IW32並不表現p53 mRNA及蛋白。 吾人建立數株可表現tsp53val135的穩定IW32細胞轉殖株。 將轉殖株培養於32.5oC,野生型(wild-type)p53表現時,細胞會先停滯於G1期,之後有的轉殖株會走向apoptosis,而有些細胞則會進行紅血球分化。 挑選傾向分化的1-5轉殖株與傾向apoptosis的3-2轉殖株,以探討p53引起apoptosis的作用機轉。 發現p53促使3-2細胞的apoptosis,伴隨著cytochrome c釋放至細胞質以及caspase-9與caspase-3的活化。 這兩個轉殖株在p53活化後p21與p27蛋白表現均增加,在傾向分化的1-5細胞其表現量明顯較3-2為多。 前處理廣效性caspase抑制劑z-VAD-fmk可抑制caspases的活化及p53所引發的apoptosis,並可促進3-2細胞p27蛋白表現量增加至與1-5細胞相當,而p21蛋白量則不受z-VAD-fmk影響。 因此,p53引發的IW32細胞apoptosis途徑包括了cytochrome c的釋放、caspases的活化與p27的分解。 在32.5℃p53表現時,可被benzidine染色的細胞增加,並且 b-globin與血質基(heme)合成酵素 d-aminolevulinic acid synthase(ALAS-E)mRNA表現明顯上升,證實p53可誘導IW32細胞分化。 Protein tyrosine phosphatase(PTPase)抑制劑sodium vanadate與phenylarsine oxide(PAO)可抑制p53誘導的細胞分化,但不影響p53所引發的生長停滯與死亡。 Sodium vanadate也會抑制p53刺激的b-globin與ALAS-E mRNA表現。 當p53活化後可偵測到細胞內PTPase活性上升,並在早期即可偵測到PTPb2與PTPe mRNA的表現,這些結果推測,PTPase似乎為p53誘發IW32細胞分化的重要因子。
綜上所述,活化的p53可抑制IW32細胞生長,並走向死亡或分化。 而p53可促使細胞釋放cytochrome c與活化caspases來引發apoptosis。 另一方面,p53所誘導的分化與 PTPase的活化有關。
The p53 tumor suppressor is a transcription factor involved in the regulation of cell cycle progression, DNA repair, differentiation and apoptosis. To dissect the p53-dependent signaling pathways, events following induction of p53 in IW32 erythroleukemia cell line were studied. IW32 cells had no detectable levels of p53 mRNA and protein expression. By transfecting a temperature-sensitive mutant p53 cDNA, tsp53val135, into the cells, several clones stably expressing the mutant p53 allele were established. At permissive temperature, these cells were growth arrested and underwent either apoptosis or differentiation. Two clones were selected for further characterization, clone 1-5 cells differentiated along the erythroid pathway and clone 3-2 cells underwent apoptosis upon wild-type p53 expression. The apoptotic response of 3-2 cells was accompanied by cytochrome c release, caspase activation as well as cleavage of caspase substrates. Levels of p21 and p27 proteins increased in both clones expressing wild type p53, with significantly greater levels of accumulation for the two proteins in clone 1-5 cells. Pretreatment of the broad spectrum caspase inhibitor z-VAD-fmk protected 3-2 cells from caspase activation and p53 induced apoptosis; and paralled with significantly elevated expression of p27 protein. p53 activation also triggered IW32 erythroleukemia cells to differentiate along the erythroid pathway, as evidenced by increased population of benzidine positive cells and elevated mRNA expression of β-globin and δ-aminolevulinic acid synthase (ALAS-E). Treatment of cells with sodium vanadate, a protein tyrosine phosphatase inhibitor, blocked the p53-induced differentiation, but not that of cell death or growth arrest. The p53 induced activation of β-globin and ALAS-E mRNA was also blocked by vanadate. Increased protein tyrosine phosphatase activity and enhanced mRNA expression of PTPβ2 and PTPε could be detected during the p53 induced IW32 cell differentiation. Together these results indicate that p53 induced multiple effects on IW32 erythroleukemia cells; the differentiation is dependent on PTPase activation whereas pathway leading to apoptosis is associated with cytochrome c release, caspase activation and p27 degradation.
封面
中文摘要
英文摘要
縮寫表
壹、緒論
1. 細胞週期(Cell cycle) 的調控
1.1 Cyclin-dependent kinases與cyclins
1.2 CDK的磷酸化與去磷酸化調控
1.3 Cyclin-deendent kinase inhibitors (CKIs)
1.4 Checkpoints與細包週期之調控
2. 程式化死亡(Apoptosis)
2.1 粒線體途徑(Mitochondrial pathway)
2.2 死亡受體之途徑(Death receptor pathway)
3. 血球分化
3.1 血紅素之生合成
3.1.1 血紅素蛋白之生合成
3.1.2 血質基之合成
4. p53腫瘤抑制蛋白
4.1 p53蛋白的結構與功能
4.1.1 Transactivation domain
4.1.2 Proline-rich domain
4.1.3 Central DNA-binding core domain
4.1.4 C端oligomerization domain
4.1.5 C端multi-functional basic domain
4.2 P53表現及活性的調控
4.2.1 轉譯
4.2.2 p53蛋白穩定性的調控
4.2.2 P53功能活性的調控
(1) 磷酸化(phosphorylation)與去磷酸化(dephosphorylation)
(2) 乙醯化(acetylation)
4.3 p53的下游效應
4.3.1 p53對細胞週期的調控
4.3.2 p53對apoptosis的調控
4.3.3 p53在DNA修補所扮演的角色
4.3.4 p53與分化的關聯
5. 細胞模式系統-IW32細胞
貳、研究動機
1. 材料
1.1 化學藥品和實驗材料
1.2 酵素和試劑
1.3 質體DNA
1.4 細胞株
1.5 探針質體
1.6 抗體
1.7 放射性物質
2. 方法
2.1 細胞培養
2.2 tsp53va1135穩定IW32細胞轉殖株的建立
2.3 Benzidine染色法
2.4 RNA的製備
2.5 北方墨點轉漬分析(Northern blot analysis)
2.6 放射免疫沉澱法(Radioimmunoprecipitation,RIP)
2.7 細胞全蛋白質的抽取
2.8 蛋白質定量法
2.9  西方墨點分析法(Western blot analysis)
2.10 質體製備
2.11 DNA片段的選殖(cloning)
2.12 Luciferase assay
2.13 流式細胞分析儀(flow cytometry analysis)
2.14 DNA梯狀踤片(DNA fragmentation)電泳的觀察
2.15 免疫螢光染色法(Immunofluorescence Assay)
2.16 Terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nickend labeling (TUNEL)測定法
2.17 PTPase活性測定
2.18 細胞內cytochrome c之分離
2.19 Caspase活性測定
肆、實驗結果
1. 建立表現p53的穩定IW32 hbt krru vfw bpru dhjd
1.1 p53基因表現的鑑定
1.2 tsp53va1135穩定轉殖株(stable transfectants)的建立
2. 確定溫度改變能表現具功能性之p53蛋白
2.1 p53活化後會由細胞質轉位至細胞核
2.2 細胞內之tsp53va1135於32.5C具有轉錄活性
3. 表現p53對IW32血癌細胞生物功能的鑑定
3.1 P53活化造成IW32血癌細胞生長停滯、死亡及分化
3.1.1 p53表現引發細胞apoptosis
3.1.2 p53所誘導之apoptosis伴隨著caspases的活化
3.1.3 Caspases抑制劑z-VAD-fink抑制p53所引發之apoptosis
3.1.4 p53所誘導之apoptosis伴隨著cytochrome c自粒線體釋出
3.1.5 p21、p27、Bax及Bc1-2於p53誘發apoptosis之變化
3.1.6 z-VAD-fmk對p21與p27表現之影響
3.2 細胞生長停滯與調控細胞週期有關基因或蛋白的變化
3.3 p53誘發IW32血癌細胞進行紅血球分化
3.3.1 Protein tyrosine phosphatase(PTPase) 抑制劑可抑制p53所誘發的分化及B-globin與ALAS-E基因的活化
3.3.2 PTPase抑制劑不影響細胞週期停滯及apoptosis
3.3.3 PTPase抑制劑不影響p21基因的活化
3.3.4 p53誘發IW32細胞分化過程中PTPase活性明顯上升
3.3.5 p53誘發IW32細胞分化時,PTPB2、PTPe mRNA被活化
伍、討論
1. P53促使IW32血癌細胞生長停滯、死亡及分化
2. P53引發IW32細胞休止於G1期的機制
3. P53引發cytochrome c釋放與活化caspases
4. Bax與apoptosis之關連
5. P21與p27在apoptosis可能扮演的角色
6. P53可誘導IW32血癌細胞分化
7. PTPase參與p53引發IW32細胞的分化
8. 結論
陸、參考文獻
柒、圖表
捌、附件一
陸、 參考文獻
Adams, J. M. and Cory, S. (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281, 1322-6.
Albrechtsen, N., Dornreiter, I., Grosse, F., Kim, E., Wiesmuller, L. and Deppert, W. (1999) Maintenance of genomic integrity by p53: complementary roles for activated and non-activated p53. Oncogene 18, 7706-17.
Almog, N. and Rotter, V. (1997) Involvement of p53 in cell differentiation and development. Biochim. Biophys. Act. 1333, F1-27.
Aoki, N., Yamaguchi-Aoki, Y. and Ullrich, A. (1996) The novel protein-tyrosine phosphatase PTP20 is a positive regulator of PC12 cell neuronal differentiation. J. Biol. Chem. 271, 29422-6.
Armstrong, J. F., Kaufman, M. H., Harrison, D. J. and Clarke, A. R. (1995) High-frequency developmental abnormalities in p53-deficient mice. Curr. Biol. 5, 931-6.
Babior, B. M. (1990) Hematology: apathophysiological approach.
Bakalkin, G., Selivanova, G., Yakovleva, T., Kiseleva, E., Kashuba, E., Magnusson, K. P., Szekely, L., Klein, G., Terenius, L. and Wiman, K. G. (1995) p53 binds single-stranded DNA ends through the C-terminal domain and internal DNA segments via the middle domain. Nucleic Acids Res. 23, 362-9.
Bakalkin, G., Yakovleva, T., Selivanova, G., Magnusson, K. P., Szekely, L., Kiseleva, E., Klein, G., Terenius, L. and Wiman, K. G. (1994) p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand transfer. Proc. Natl. Acad. Sci. USA 91, 413-7.
Baldassarre, G., Barone, M. V., Belletti, B., Sandomenico, C., Bruni, P., Spiezia, S., Boccia, A., Vento, M. T., Romano, A., Pepe, S., Fusco, A. and Viglietto, G. (1999) Key role of the cyclin-dependent kinase inhibitor p27kip1 for embryonal carcinoma cell survival and differentiation. Oncogene 18, 6241-51.
Banin, S., Moyal, L., Shieh, S., Taya, Y., Anderson, C. W., Chessa, L., Smorodinsky, N. I., Prives, C., Reiss, Y., Shiloh, Y. and Ziv, Y. (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281, 1674-7.
Bates, S. and Vousden, K. H. (1999) Mechanisms of p53-mediated apoptosis. Cell Mol. Life. Sci. 55, 28-37.
Baudier, J., Delphin, C., Grunwald, D., Khochbin, S. and Lawrence, J. J. (1992) Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein. Proc. Natl. Acad. Sci. USA 89, 11627-31.
Bayle, J. H., Elenbaas, B. and Levine, A. J. (1995) The carboxyl-terminal domain of the p53 protein regulates sequence-specific DNA binding through its nonspecific nucleic acid-binding activity. Proc. Natl. Acad. Sci. USA. 92, 5729-33.
Ben-David, Y. and Bernstein, A. (1991) Friend virus-induced erythroleukemia and the multistage nature of cancer. Cell 66, 831-4.
Ben-David, Y., Lavigueur, A., Cheong, G. Y. and Bernstein, A. (1990) Insertional inactivation of the p53 gene during friend leukemia: a new strategy for identifying tumor suppressor genes. New Biol. 2, 1015-23.
Beru, N., Maples, P. B., Hermine, O. and Goldwasser, E. (1990). Differential expression of alpha- and beta-globin genes in erythroleukemic cell lines. Mol. Cell Biol. 10, 3591-5.
Bischoff, J. R., Friedman, P. N., Marshak, D. R., Prives, C. and Beach, D. (1990) Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc. Natl. Acad. Sci. USA 87, 4766-70.
Bissonnette, N., Wasylyk, B. and Hunting, D. J. (1997) The apoptotic and transcriptional transactivation activities of p53 can be dissociated. Biochem. Cell Biol. 75, 351-8.
Booher, R. N., Holman, P. S. and Fattaey, A. (1997) Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity. J. Biol. Chem. 272, 22300-6.
Brady, H. J., Salomons, G. S., Bobeldijk, R. C. and Berns, A. J. (1996) T cells from baxalpha transgenic mice show accelerated apoptosis in response to stimuli but do not show restored DNA damage-induced cell death in the absence of p53. gene product in. EMBO J. 15, 1221-30.
Brain, R. and Jenkins, J. R. (1994) Human p53 directs DNA strand reassociation and is photolabelled by 8-azido ATP. Oncogene 9, 1775-80.
Bratton, S. B., MacFarlane, M., Cain, K. and Cohen, G. M. (2000) Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Exp. Cell Res. 256, 27-33.
Brown, J. P., Wei, W. and Sedivy, J. M. (1997) Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277, 831-4.
Brugarolas, J., Chandrasekaran, C., Gordon, J. I., Beach, D., Jacks, T. and Hannon, G. J. (1995) Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377, 552-7.
Buckbinder, L., Talbott, R., Velasco-Miguel, S., Takenaka, I., Faha, B., Seizinger, B. R. and Kley, N. (1995) Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature 377, 646-9.
Budihardjo, I., Oliver, H., Lutter, M., Luo, X. and Wang, X. (1999) Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell. Dev. Biol. 15, 269-90.
Burand, J. P. and Lu, H. (1997) Replication of a Gonad-Specific Insect Virus in TN-368 Cells in Culture. J. Invertebr. Pathol. 70, 88-95.
Burma, S., Kurimasa, A., Xie, G., Taya, Y., Araki, R., Abe, M., Crissman, H. A., Ouyang, H., Li, G. C. and Chen, D. J. (1999) DNA-dependent protein kinase-independent activation of p53 in response to DNA damage. J. Biol. Chem. 274, 17139-43.
Caelles, C., Helmberg, A. and Karin, M. (1994) p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature 370, 220-3.
Canman, C. E., Lim, D. S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B. and Siliciano, J. D. (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281, 1677-9.
Carr, A. M. (2000) Cell cycle. Piecing together the p53 puzzle. Science 287, 1765-6.
Casaccia-Bonnefil, P., Tikoo, R., Kiyokawa, H., Friedrich, V., Jr., Chao, M. V. and Koff, A. (1997) Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. Genes Dev. 11, 2335-46.
Caspari, T. (2000) How to activate p53. Curr. Biol. 10, R315-7.
Chan, T. A., Hermeking, H., Lengauer, C., Kinzler, K. W. and Vogelstein, B. (1999) 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature 401, 616-20.
Chaturvedi, P., Eng, W. K., Zhu, Y., Mattern, M. R., Mishra, R., Hurle, M. R., Zhang, X., Annan, R. S., Lu, Q., Faucette, L. F., Scott, G. F., Li, X., Carr, S. A., Johnson, R. K., Winkler, J. D. and Zhou, B. B. (1999) Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Oncogene 18, 4047-54.
Chehab, N. H., Malikzay, A., Appel, M. and Halazonetis, T. D. (2000) Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev. 14, 278-88.
Chehab, N. H., Malikzay, A., Stavridi, E. S. and Halazonetis, T. D. (1999) Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc. Natl. Acad. Sci. USA 96, 13777-82.
Chen, X., Ko, L. J., Jayaraman, L. and Prives, C. (1996) p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev. 10, 2438-51.
Cho, Y., Gorina, S., Jeffrey, P. D. and Pavletich, N. P. (1994) Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265, 346-55.
Choppin, J., Lacombe, C., Casadevall, N., Muller, O., Tambourin, P. and Varet, B. (1984) Characterization of erythropoietin produced by IW32 murine erythroleukemia cells. Blood 64, 341-7.
Chow, V., Ben-David, Y., Bernstein, A., Benchimol, S. and Mowat, M. (1987) Multistage Friend erythroleukemia: independent origin of tumor clones with normal or rearranged p53 cellular oncogenes. J Virol. 61, 2777-81.
Chylicki, K., Ehinger, M., Svedberg, H. and Gullberg, U. (2000) Characterization of the molecular mechanisms for p53-mediated differentiation. Cell Growth Differ. 11, 561-71.
Clarke, M. F., Kukowska-Latallo, J. F., Westin, E., Smith, M. and Prochownik, E. V. (1988) Constitutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation. Mol. Cell. Biol. 8, 884-92.
Cross, S. M., Sanchez, C. A., Morgan, C. A., Schimke, M. K., Ramel, S., Idzerda, R. L., Raskind, W. H. and Reid, B. J. (1995) A p53-dependent mouse spindle checkpoint. Science 267, 1353-6.
Crossley, M. and Orkin, S. H. (1993) Regulation of the beta-globin locus. Curr. Opin. Genet. Dev. 3, 232-7.
Deng, C., Zhang, P., Harper, J. W., Elledge, S. J. and Leder, P. (1995) Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell 82, 675-84.
Donehower, L. A. (1996) The p53-deficient mouse: a model for basic and applied cancer studies. Semin. Cancer Biol. 7, 269-78.
Dotto, G. P. (2000). p21(WAF1/Cip1) more than a break to the cell cycle? Biochim. Biophys. Acta 1471, M43-56.
Dragovich, T., Rudin, C. M. and Thompson, C. B. (1998) Signal transduction pathways that regulate cell survival and cell death. Oncogene 17, 3207-13.
Dumaz, N. and Meek, D. W. (1999) Serine15 phosphorylation stimulates p53 transactivation but does not directly influence interaction with HDM2. EMBO J. 18, 7002-10.
Durand, B., Gao, F. B. and Raff, M. (1997) Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J. 16, 306-17.
Ehinger, M., Bergh, G., Johnsson, E., Baldetorp, B., Olsson, I. and Gullberg, U. (1998) p53-dependent and -independent differentiation of leukemic U-937 cells: relationship to cell cycle control. Exp. Hematol. 26, 1043-52.
Ehinger, M., Bergh, G., Johnsson, E., Gullberg, U. and Olsson, I. (1997) The tumor suppressor gene p53 can mediate transforming growth [corrected] factor beta1-induced differentiation of leukemic cells independently of activation of the retinoblastoma protein. Cell Growth Differ. 8, 1127-37.
Eizenberg, O., Faber-Elman, A., Gottlieb, E., Oren, M., Rotter, V. and Schwartz, M. (1996) p53 plays a regulatory role in differentiation and apoptosis of central nervous system-associated cells. Mol. Cell. Biol. 16, 5178-85.
el-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W. and Vogelstein, B. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817-25.
Elledge, S. J. (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274, 1664-72.
Eymin, B., Haugg, M., Droin, N., Sordet, O., Dimanche-Boitrel, M. T. and Solary, E. (1999) p27Kip1 induces drug resistance by preventing apoptosis upstream of cytochrome c release and procaspase-3 activation in leukemic cells. Oncogene 18, 1411-8.
Feinstein, E., Gale, R. P., Reed, J. and Canaani, E. (1992) Expression of the normal p53 gene induces differentiation of K562 cells. Oncogene 7, 1853-7.
Fero, M. L., Rivkin, M., Tasch, M., Porter, P., Carow, C. E., Firpo, E., Polyak, K., Tsai, L. H., Broudy, V., Perlmutter, R. M., Kaushansky, K. and Roberts, J. M. (1996) A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 85, 733-44.
Finucane, D. M., Bossy-Wetzel, E., Waterhouse, N. J., Cotter, T. G. and Green, D. R. (1999) Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL. J. Biol. Chem. 274, 2225-33.
Finucane, D. M., Bossy-Wetzel, E., Waterhouse, N. J., Cotter, T. G. and Green, D. R. (1999) Bax-induced caspase activation and apoptosis via cytochrome c release from mitochondria is inhibitable by Bcl-xL. J. Biol. Chem. 274, 2225-33.
Friedlander, P., Haupt, Y., Prives, C. and Oren, M. (1996) A mutant p53 that discriminates between p53-responsive genes cannot induce apoptosis. Mol. Cell. Biol. 16, 4961-71.
Friedman, S. L., Shaulian, E., Littlewood, T., Resnitzky, D. and Oren, M. (1997) Resistance to p53-mediated growth arrest and apoptosis in Hep 3B hepatoma cells. Oncogene 15, 63-70.
Fu, L. and Benchimol, S. (1997) Participation of the human p53 3''UTR in translational repression and activation following gamma-irradiation. EMBO J. 16, 4117-25.
Fujita, H., Yamamoto, M., Yamagami, T., Hayashi, N. and Sassa, S. (1991) Erythroleukemia differentiation. Distinctive responses of the erythroid-specific and the nonspecific delta-aminolevulinate synthase mRNA. J. Biol. Chem. 266, 17494-502.
Fujiwara, Y., Browne, C. P., Cunniff, K., Goff, S. C. and Orkin, S. H. (1996) Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proc. Natl. Acad. Sci. USA 93, 12355-8.
Furnari, B., Rhind, N. and Russell, P. (1997) Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science 277, 1495-7.
Gervais, J. L., Seth, P. and Zhang, H. (1998) Cleavage of CDK inhibitor p21(Cip1/Waf1) by caspases is an early event during DNA damage-induced apoptosis. J. Biol. Chem. 273, 19207-12.
Ghebranious, N. and Donehower, L. A. (1998) Mouse models in tumor suppression. Oncogene 17, 3385-400.
Giaccia, A. J. and Kastan, M. B. (1998) The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev. 12, 2973-83.
Gil-Gomez, G., Berns, A. and Brady, H. J. (1998) A link between cell cycle and cell death: Bax and Bcl-2 modulate Cdk2 activation during thymocyte apoptosis. EMBO J. 17, 7209-18.
Girard, F., Strausfeld, U., Fernandez, A. and Lamb, N. J. (1991) Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell 67, 1169-79.
Godin, I. E., Garcia-Porrero, J. A., Coutinho, A., Dieterlen-Lievre, F. and Marcos, M. A. (1993) Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors. Nature 364, 67-70.
Gorospe, M., Cirielli, C., Wang, X., Seth, P., Capogrossi, M. C. and Holbrook, N. J. (1997) p21(Waf1/Cip1) protects against p53-mediated apoptosis of human melanoma cells. Oncogene 14, 929-35.
Gorospe, M., Wang, X., Guyton, K. Z. and Holbrook, N. J. (1996) Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells. Mol. Cell. Biol. 16, 6654-60.
Gottlieb, E. and Oren, M. (1998) p53 facilitates pRb cleavage in IL-3-deprived cells: novel pro-apoptotic activity of p53. EMBO J. 17, 3587-96.
Gottlieb, T. M. and Oren, M. (1996) p53 in growth control and neoplasia. Biochim. Biophys. Acta. 1287, 77-102.
Gross, A., Jockel, J., Wei, M. C. and Korsmeyer, S. J. (1998) Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J. 17, 3878-85.
Gross, A., McDonnell, J. M. and Korsmeyer, S. J. (1999a) BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-911.
Gross, A., Yin, X. M., Wang, K., Wei, M. C., Jockel, J., Milliman, C., Erdjument-Bromage, H., Tempst, P. and Korsmeyer, S. J. (1999b) Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death. J. Biol. Chem. 274, 1156-63.
Gu, W. and Roeder, R. G. (1997a) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90, 595-606.
Gu, W., Shi, X. L. and Roeder, R. G. (1997b) Synergistic activation of transcription by CBP and p53. Nature 387, 819-23.
Guillouf, C., Rosselli, F., Sjin, R. T., Moustacchi, E., Hoffman, B. and Liebermann, D. A. (1998) Role of a mutant p53 protein in apoptosis: characterization of a function independent of transcriptional trans-activation. Int. J. Oncol. 13, 107-14.
Hakem, A., Sasaki, T., Kozieradzki, I. and Penninger, J. M. (1999) The cyclin-dependent kinase Cdk2 regulates thymocyte apoptosis. J. Exp. Med. 189, 957-68.
Halevy, O., Novitch, B. G., Spicer, D. B., Skapek, S. X., Rhee, J., Hannon, G. J., Beach, D. and Lassar, A. B. (1995) Correlation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science 267, 1018-21.
Han, Z., Bhalla, K., Pantazis, P., Hendrickson, E. A. and Wyche, J. H. (1999) Cif (Cytochrome c efflux-inducing factor) activity is regulated by Bcl-2 and caspases and correlates with the activation of Bid. Mol. Cell. Biol. 19, 1381-9.
Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K. and Elledge, S. J. (1993) The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75, 805-16.
Haupt, Y., Rowan, S. and Oren, M. (1995) p53-mediated apoptosis in HeLa cells can be overcome by excess pRB. Oncogene 10, 1563-71.
Heath, D. S., Axelrad, A. A., McLeod, D. L. and Shreeve, M. M. (1976) Separation of the erythropoietin-responsive progenitors BFU-E and CFU-E in mouse bone marrow by unit gravity sedimentation. Blood 47, 777-92.
Hermeking, H., Lengauer, C., Polyak, K., He, T. C., Zhang, L., Thiagalingam, S., Kinzler, K. W. and Vogelstein, B. (1997) 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol. Cell 1, 3-11.
Herrmann, M., Lorenz, H. M., Voll, R., Grunke, M., Woith, W. and Kalden, J. R. (1994) A rapid and simple method for the isolation of apoptotic DNA fragments. Nucleic Acids Res. 22, 5506-7.
Hirao, A., Kong, Y. Y., Matsuoka, S., Wakeham, A., Ruland, J., Yoshida, H., Liu, D., Elledge, S. J. and Mak, T. W. (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287, 1824-7.
Hirao, A., Kong, Y. Y., Matsuoka, S., Wakeham, A., Ruland, J., Yoshida, H., Liu, D., Elledge, S. J. and Mak, T. W. (2000) DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287, 1824-7.
Hiromura, K., Pippin, J. W., Fero, M. L., Roberts, J. M. and Shankland, S. J. (1999) Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). J. Clin. Invest. 103, 597-604.
Hiromura, K., Pippin, J. W., Fero, M. L., Roberts, J. M. and Shankland, S. J. (1999) Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). J. Clin. Invest. 103, 597-604.
Hollstein, M., Rice, K., Greenblatt, M. S., Soussi, T., Fuchs, R., Sorlie, T., Hovig, E., Smith-Sorensen, B., Montesano, R. and Harris, C. C. (1994) Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res. 22, 3551-5.
Horikoshi, N., Usheva, A., Chen, J., Levine, A. J., Weinmann, R. and Shenk, T. (1995) Two domains of p53 interact with the TATA-binding protein, and the adenovirus 13S E1A protein disrupts the association, relieving p53-mediated transcriptional repression. Mol. Cell. Biol. 15, 227-34.
Hu, Y., Benedict, M. A., Wu, D., Inohara, N. and Nunez, G. (1998) Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc. Natl. Acad. Sci. USA 95, 4386-91.
Hupp, T. R., Meek, D. W., Midgley, C. A. and Lane, D. P. (1993) Activation of the cryptic DNA binding function of mutant forms of p53. Nucleic Acids Res. 21, 3167-74.
Hupp, T. R., Sparks, A. and Lane, D. P. (1995) Small peptides activate the latent sequence-specific DNA binding function of p53. Cell 83, 237-45.
Jiang, H., Lin, J., Su, Z. Z., Collart, F. R., Huberman, E. and Fisher, P. B. (1994) Induction of differentiation in human promyelocytic HL-60 leukemia cells activates p21, WAF1/CIP1, expression in the absence of p53. Oncogene 9, 3397-406.
Jin, Y. H., Yoo, K. J., Lee, Y. H. and Lee, S. K. (2000) Caspase 3-mediated cleavage of p21WAF1/CIP1 associated with the cyclin A-cyclin-dependent kinase 2 complex is a prerequisite for apoptosis in SK-HEP-1 cells. J. Biol. Chem. 275, 30256-63.
Johnson, D. G. and Walker, C. L. (1999) Cyclins and cell cycle checkpoints. Annu. Rev. Pharmacol. Toxicol. 39, 295-312.
Johnson, P., Chung, S. and Benchimol, S. (1993) Growth suppression of Friend virus-transformed erythroleukemia cells by p53 protein is accompanied by hemoglobin production and is sensitive to erythropoietin. Mol. Cell. Biol. 13, 1456-63.
Kapoor, M. and Lozano, G. (1998) Functional activation of p53 via phosphorylation following DNA damage by UV but not gamma radiation. Proc. Natl. Acad. Sci. USA 95, 2834-7.
Kastan, M. B., Stone, K. D. and Civin, C. I. (1989) Nuclear oncoprotein expression as a function of lineage, differentiation stage, and proliferative status of normal human hematopoietic cells. Blood 74, 1517-24.
Kastan, M. B., Zhan, Q., el-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B. and Fornace, A. J., Jr. (1992) A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71, 587-97.
Kelekar, A., Chang, B. S., Harlan, J. E., Fesik, S. W. and Thompson, C. B. (1997) Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. Mol. Cell. Biol. 17, 7040-6.
Kitada, S., Krajewski, S., Miyashita, T., Krajewska, M. and Reed, J. C. (1996) Gamma-radiation induces upregulation of Bax protein and apoptosis in radiosensitive cells in vivo. Oncogene 12, 187-92.
Kiyokawa, H., Kineman, R. D., Manova-Todorova, K. O., Soares, V. C., Hoffman, E. S., Ono, M., Khanam, D., Hayday, A. C., Frohman, L. A. and Koff, A. (1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 85, 721-32.
Kluck, R. M., Bossy-Wetzel, E., Green, D. R. and Newmeyer, D. D. (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132-6.
Kluck, R. M., Bossy-Wetzel, E., Green, D. R. and Newmeyer, D. D. (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275, 1132-6.
Knudson, C. M., Tung, K. S., Tourtellotte, W. G., Brown, G. A. and Korsmeyer, S. J. (1995) Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 270, 96-9.
Ko, L. J. and Prives, C. (1996).p53: puzzle and paradigm. Genes Dev. 10, 1054-72.
Ko, L. J., Shieh, S. Y., Chen, X., Jayaraman, L., Tamai, K., Taya, Y., Prives, C. and Pan, Z. Q. (1997) p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner. Mol. Cell. Biol. 17, 7220-9.
Kranenburg, O., de Groot, R. P., Van der Eb, A. J. and Zantema, A. (1995) Differentiation of P19 EC cells leads to differential modulation of cyclin-dependent kinase activities and to changes in the cell cycle profile. Oncogene 10, 87-95.
Kroemer, G., Dallaporta, B. and Resche-Rigon, M. (1998) The mitochondrial death/life regulator in apoptosis and necrosis. Annu. Rev. Physiol. 60, 619-42.
Kume, T., Tsuneizumi, K., Watanabe, T., Thomas, M. L. and Oishi, M. (1994) Induction of specific protein tyrosine phosphatase transcripts during differentiation of mouse erythroleukemia cells. J. Biol. Chem. 269, 4709-12.
Kume, T., Watanabe, T., Sanokawo, R., Chida, D., Nakamura, T. and Oishi, M (1996). Expression of the protein tyrosine phosphatase beta2 gene in mouse erythroleukemia cells induces terminal erythroid differentiation. J. Biol. Chem. 271, 30916-21.
Lambert, P. F., Kashanchi, F., Radonovich, M. F., Shiekhattar, R. and Brady, J. N (1998). Phosphorylation of p53 serine 15 increases interaction with CBP. J. Biol. Chem. 273, 33048-53.
LaMontagne, K. R., Jr., Flint, A. J., Franza, B. R., Jr., Pandergast, A. M. and Tonks, N. K. (1998a) Protein tyrosine phosphatase 1B antagonizes signalling by oncoprotein tyrosine kinase p210 bcr-abl in vivo. Mol. Cell. Biol. 18, 2965-75.
LaMontagne, K. R., Jr., Hannon, G. and Tonks, N. K. (1998b) Protein tyrosine phosphatase PTP1B suppresses p210 bcr-abl-induced transformation of rat-1 fibroblasts and promotes differentiation of K562 cells. Proc. Natl. Acad. Sci. USA 95, 14094-9.
Laronga, C., Yang, H. Y., Neal, C. and Lee, M. H. (2000) Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J. Biol. Chem. 275, 23106-12.
Lee, M. H., Reynisdottir, I. and Massague, J. (1995) Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev. 9, 639-49.
Lee, S., Cavallo, L. and Griffith, J. (1997) Human p53 binds Holliday junctions strongly and facilitates their cleavage. J. Biol. Chem. 272, 7532-9.
Lee, S., Elenbaas, B., Levine, A. and Griffith, J. (1995) p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches. Cell 81, 1013-20.
Lees-Miller, S. P., Chen, Y. R. and Anderson, C. W. (1990) Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen. Mol. Cell. Biol. 10, 6472-81.
Leveillard, T., Andera, L., Bissonnette, N., Schaeffer, L., Bracco, L., Egly, J. M. and Wasylyk, B. (1996) Functional interactions between p53 and the TFIIH complex are affected by tumour-associated mutations. EMBO J. 15, 1615-24.
Levine, A. J. (1997) p53, the cellular gatekeeper for growth and division. Cell 88, 323-31.
Levkau, B., Koyama, H., Raines, E. W., Clurman, B. E., Herren, B., Orth, K., Roberts, J. M. and Ross, R. (1998) Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade. Mol. Cell 1, 553-63.
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S. and Wang, X. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-89.
Li, P. F., Dietz, R. and von Harsdorf, R. (1999) p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2. EMBO J. 18, 6027-36.
Lin, J., Chen, J., Elenbaas, B. and Levine, A. J. (1994) Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev. 8, 1235-46.
Lin, Y., Ma, W. and Benchimol, S. (2000) Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosis. Nat. Genet. 26, 122-7.
Liu, F., Stanton, J. J., Wu, Z. and Piwnica-Worms, H. (1997) The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Mol. Cell. Biol. 17, 571-83.
Liu, M., Lee, M. H., Cohen, M., Bommakanti, M. and Freedman, L. P. (1996) Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 10, 142-53.
Livingstone, L. R., White, A., Sprouse, J., Livanos, E., Jacks, T. and Tlsty, T. D. (1992) Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70, 923-35.
Lozano, G. and Liu, G. (1998) Mouse models dissect the role of p53 in cancer and development. Semin. Cancer Biol. 8, 337-44.
Lu, H. and Levine, A. J. (1995) Human TAFII31 protein is a transcriptional coactivator of the p53 protein. Proc. Natl. Acad. Sci. USA 92, 5154-8.
Lu, H., Taya, Y., Ikeda, M. and Levine, A. J. (1998) Ultraviolet radiation, but not gamma radiation or etoposide-induced DNA damage, results in the phosphorylation of the murine p53 protein at serine-389. Proc. Natl. Acad. Sci. USA 95, 6399-402.
Matsuoka, S., Huang, M. and Elledge, S. J. (1998) Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 282, 1893-7.
Mazzaro, G., Bossi, G., Coen, S., Sacchi, A. and Soddu, S. (1999) The role of wild-type p53 in the differentiation of primary hemopoietic and muscle cells. Oncogene 18, 5831-5.
Meikrantz, W. and Schlegel, R. (1996) Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases. J. Biol. Chem. 271, 10205-9.
Michalovitz, D., Halevy, O. and Oren, M. (1990) Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell 62, 671-80.
Milne, D. M., Palmer, R. H., Campbell, D. G. and Meek, D. W. (1992) Phosphorylation of the p53 tumour-suppressor protein at three N-terminal sites by a novel casein kinase I-like enzyme. Oncogene 7, 1361-9.
Miyashita, T., Harigai, M., Hanada, M. and Reed, J. C. (1994) Identification of a p53-dependent negative response element in the bcl-2 gene. Cancer Res. 54, 3131-5.
Miyashita, T. and Reed, J. C. (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293-9.
Mosner, J., Mummenbrauer, T., Bauer, C., Sczakiel, G., Grosse, F. and Deppert, W. (1995) Negative feedback regulation of wild-type p53 biosynthesis. EMBO J. 14, 4442-9.
Muller-Tiemann, B. F., Halazonetis, T. D. and Elting, J. J. (1998) Identification of an additional negative regulatory region for p53 sequence-specific DNA binding. Proc. Natl. Acad. Sci. USA 95, 6079-84.
Murphy, M., Hinman, A. and Levine, A. J. (1996) Wild-type p53 negatively regulates the expression of a microtubule-associated protein. Genes Dev. 10, 2971-80.
Nakano, K. and Vousden, K. H. (2001) PUMA, a novel proapoptotic gene is induced by p53. Mol. Cell 7, 683-94.
Nakayama, K., Ishida, N., Shirane, M., Inomata, A., Inoue, T., Shishido, N., Horii, I. and Loh, D. Y. (1996) Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85, 707-20.
Nasmyth, K. (1996) Viewpoint: putting the cell cycle in order. Science 274, 1643-5.
Niculescu, A. B., 3rd, Chen, X., Smeets, M., Hengst, L., Prives, C. and Reed, S. I. (1998) Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol. Cell. Biol. 18, 629-43.
Noda, A., Ning, Y., Venable, S. F., Pereira-Smith, O. M. and Smith, J. R. (1994) Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp. Cell Res. 211, 90-8.
Nuez, B., Michalovich, D., Bygrave, A., Ploemacher, R. and Grosveld, F. (1995) Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature 375, 316-8.
O''Connell, M. J., Walworth, N. C. and Carr, A. M. (2000 The G2-phase DNA-damage checkpoint. Trends Cell Biol. 10, 296-303
Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T. and Tanaka, N. (2000a) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288, 1053-8.
Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y. and Taya, Y. (2000b) p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102, 849-62.
Offerhaus, G. J., Giardiello, F. M., Bruijn, J. A., Stijnen, T., Molyvas, E. N. and Fleuren, G. J. (1991) The value of immunohistochemistry for collagen IV expression in colorectal carcinomas. Cancer 67, 99-105.
Ohki, R., Nemoto, J., Murasawa, H., Oda, E., Inazawa, J., Tanaka, N. and Taniguchi, T. (2000) Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase. J. Biol. Chem. 275, 22627-30.
Ohtsubo, M., Theodoras, A. M., Schumacher, J., Roberts, J. M. and Pagano, M. (1995) Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol. Cell. Biol. 15, 2612-24.
Orkin, S. H. (1992) GATA-binding transcription factors in hematopoietic cells. Blood 80, 575-81.
Orkin, S. H. (1995) Transcription factors and hematopoietic development. J. Biol. Chem. 270, 4955-8.
Ottilie, S., Diaz, J. L., Horne, W., Chang, J., Wang, Y., Wilson, G., Chang, S., Weeks, S., Fritz, L. C. and Oltersdorf, T. (1997) Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins. J. Biol. Chem. 272, 30866-72.
Owen-Schaub, L. B., Zhang, W., Cusack, J. C., Angelo, L. S., Santee, S. M., Fujiwara, T., Roth, J. A., Deisseroth, A. B., Zhang, W. W., Kruzel, E. and et al. (1995) Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol. Cell. Biol. 15, 3032-40.
Pan, G., O''Rourke, K. and Dixit, V. M. (1998) Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. J. Biol. Chem. 273, 5841-5.
Park, D. S., Farinelli, S. E. and Greene, L. A. (1996) Inhibitors of cyclin-dependent kinases promote survival of post-mitotic neuronally differentiated PC12 cells and sympathetic neurons. J. Biol. Chem. 271, 8161-9.
Parker, S. B., Eichele, G., Zhang, P., Rawls, A., Sands, A. T., Bradley, A., Olson, E. N., Harper, J. W. and Elledge, S. J. (1995) p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science 267, 1024-7.
Peng, C. Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S. and Piwnica-Worms, H. (1997) Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 277, 1501-5.
Perkins, A. C., Sharpe, A. H. and Orkin, S. H. (1995) Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature 375, 318-22.
Pevny, L., Simon, M. C., Robertson, E., Klein, W. H., Tsai, S. F., D''Agati, V., Orkin, S. H. and Costantini, F. (1991) Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349, 257-60.
Poluha, W., Poluha, D. K., Chang, B., Crosbie, N. E., Schonhoff, C. M., Kilpatrick, D. L. and Ross, A. H. (1996) The cyclin-dependent kinase inhibitor p21 (WAF1) is required for survival of differentiating neuroblastoma cells. Mol. Cell. Biol. 16, 1335-41.
Polyak, K., Xia, Y., Zweier, J. L., Kinzler, K. W. and Vogelstein, B. (1997) A model for p53-induced apoptosis. Nature 389, 300-5.
Ponka, P. (1997) Tissue-specific regulation of iron metabolism and heme synthesis: distinct control mechanisms in erythroid cells. Blood 89, 1-25.
Price, B. D., Hughes-Davies, L. and Park, S. J. (1995) Cdk2 kinase phosphorylates serine 315 of human p53 in vitro. Oncogene 11, 73-80.
Prisco, M., Hongo, A., Rizzo, M. G., Sacchi, A. and Baserga, R. (1997) The insulin-like growth factor I receptor as a physiologically relevant target of p53 in apoptosis caused by interleukin-3 withdrawal. Mol. Cell. Biol. 17, 1084-92.
Prives, C. (1998) Signaling to p53: breaking the MDM2-p53 circuit. Cell 95, 5-8.
Profous-Juchelka, H. R., Reuben, R. C., Marks, P. A. and Rifkind, R. A. (1983) Transcriptional and post-transcriptional regulation of globin gene accumulation in murine erythroleukemia cells. Mol. Cell. Biol. 3, 229-32.
Rajah, R., Valentinis, B. and Cohen, P. (1997) Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism. J. Biol. Chem. 272, 12181-8.
Reed, M., Woelker, B., Wang, P., Wang, Y., Anderson, M. E. and Tegtmeyer, P. (1995) The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation. Proc. Natl. Acad. Sci. USA 92, 9455-9.
Reynaud, E. G., Leibovitch, M. P., Tintignac, L. A., Pelpel, K., Guillier, M. and Leibovitch, S. A. (2000) Stabilization of MyoD by direct binding to p57(Kip2). J. Biol. Chem. 275, 18767-76.
Riddle, R. D., Yamamoto, M. and Engel, J. D. (1989) Expression of delta-aminolevulinate synthase in avian cells: separate genes encode erythroid-specific and nonspecific isozymes. Proc. Natl. Acad. Sci. USA 86, 792-6.
Robertson, J. D., Orrenius, S. and Zhivotovsky, B. (2000) Review: nuclear events in apoptosis. J. Struct. Biol. 129, 346-58.
Romana, M., Dubart, A., Beaupain, D., Chabret, C., Goossens, M. and Romeo, P. H. (1987) Structure of the gene for human uroporphyrinogen decarboxylase. Nucleic Acids Res. 15, 7343-56.
Ronen, D., Schwartz, D., Teitz, Y., Goldfinger, N. and Rotter, V. (1996) Induction of HL-60 cells to undergo apoptosis is determined by high levels of wild-type p53 protein whereas differentiation of the cells is mediated by lower p53 levels. Cell Growth Differ. 7, 21-30.
Rotter, V., Schwartz, D., Almon, E., Goldfinger, N., Kapon, A., Meshorer, A., Donehower, L. A. and Levine, A. J. (1993) Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome. Proc. Natl. Acad. Sci. USA 90, 9075-9.
Sabbatini, P., Chiou, S. K., Rao, L. and White, E. (1995) Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein. Mol. Cell. Biol. 15, 1060-70.
Sah, V. P., Attardi, L. D., Mulligan, G. J., Williams, B. O., Bronson, R. T. and Jacks, T. (1995) A subset of p53-deficient embryos exhibit exencephaly. Nat. Genet.10, 175-80.
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W. and Appella, E. (1998) DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev. 12, 2831-41.
Sakaguchi, K., Sakamoto, H., Lewis, M. S., Anderson, C. W., Erickson, J. W., Appella, E. and Xie, D. (1997) Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36, 10117-24.
Sakaguchi, K., Sakamoto, H., Lewis, M. S., Anderson, C. W., Erickson, J. W., Appella, E. and Xie, D. (1997) Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36, 10117-24.
Schlesinger, P. H., Gross, A., Yin, X. M., Yamamoto, K., Saito, M., Waksman, G. and Korsmeyer, S. J. (1997) Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2. Proc. Natl. Acad. Sci. USA 94, 11357-62.
Schmidt, T., Korner, K., Karsunky, H., Korsmeyer, S., Muller, R. and Moroy, T. (1999) The activity of the murine Bax promoter is regulated by Sp1/3 and E-box binding proteins but not by p53. Cell Death Differ. 6, 873-82.
Schneider, E., Montenarh, M. and Wagner, P. (1998) Regulation of CAK kinase activity by p53. Oncogene 17, 2733-41.
Sgambato, A., Cittadini, A., Faraglia, B. and Weinstein, I. B. (2000) Multiple functions of p27(Kip1) and its alterations in tumor cells: a review. J. Cell Physiol. 183, 18-27.
Shaulsky, G., Goldfinger, N., Peled, A. and Rotter, V. (1991) Involvement of wild-type p53 in pre-B-cell differentiation in vitro. Proc. Natl. Acad. Sci. USA 88, 8982-6.
Sherr, C. J. (1994) G1 phase progression: cycling on cue. Cell 79, 551-5.
Sherr, C. J. and Roberts, J. M. (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501-12.
Sherr, C. J. and Roberts, J. M. (1995) Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9, 1149-63.
Sherr, C. J. and Weber, J. D. (2000) The ARF/p53 pathway. Curr. Opin. Genet. Dev. 10, 94-9.
Shi, L., Chen, G., He, D., Bosc, D. G., Litchfield, D. W. and Greenberg, A. H. (1996 Granzyme B induces apoptosis and cyclin A-associated cyclin-dependent kinase activity in all stages of the cell cycle. J. Immunol. 157, 2381-5.
Shiah, S. G., Chuang, S. E., Chau, Y. P., Shen, S. C. and Kuo, M. L. (1999) Activation of c-Jun NH2-terminal kinase and subsequent CPP32/Yama during topoisomerase inhibitor beta-lapachone-induced apoptosis through an oxidation-dependent pathway. Cancer Res. 59, 391-8.
Shieh, S. Y., Ahn, J., Tamai, K., Taya, Y. and Prives, C. (2000) The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 14, 289-300.
Shieh, S. Y., Ikeda, M., Taya, Y. and Prives, C. (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91, 325-34.
Shieh, S. Y., Taya, Y. and Prives, C. (1999) DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization. EMBO J. 18, 1815-23.
Shimizu, A., Nishida, J., Ueoka, Y., Kato, K., Hachiya, T., Kuriaki, Y. and Wake, N. (1998) CyclinG contributes to G2/M arrest of cells in response to DNA damage. Biochem. Biophys. Res. Commun. 242, 529-33.
Shimizu, S., Eguchi, Y., Kamiike, W., Waguri, S., Uchiyama, Y., Matsuda, H. and Tsujimoto, Y. (1996) Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors. Oncogene 13, 21-9.
Shivakumar, C. V., Brown, D. R., Deb, S. and Deb, S. P. (1995) Wild-type human p53 transactivates the human proliferating cell nuclear antigen promoter. Mol. Cell. Biol. 15, 6785-93.
Shivdasani, R. A. and Orkin, S. H. (1996) The transcriptional control of hematopoiesis. Blood 87, 4025-39.
Siliciano, J. D., Canman, C. E., Taya, Y., Sakaguchi, K., Appella, E. and Kastan, M. B. (1997) DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev. 11, 3471-81.
Sionov, R. V. and Haupt, Y. (1999) The cellular response to p53: the decision between life and death. Oncogene 18, 6145-57.
Skapek, S. X., Rhee, J., Spicer, D. B. and Lassar, A. B. (1995) Inhibition of myogenic differentiation in proliferating myoblasts by cyclin D1-dependent kinase. Science 267, 1022-4.
Slingerland, J. and Pagano, M. (2000) Regulation of the cdk inhibitor p27 and its deregulation in cancer. J. Cell Physiol. 183, 10-7.
Smith, M. L., Chen, I. T., Zhan, Q., Bae, I., Chen, C. Y., Gilmer, T. M., Kastan, M. B., O''Connor, P. M. and Fornace, A. J., Jr. (1994) Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science 266, 1376-80.
Smits, V. A., Klompmaker, R., Vallenius, T., Rijksen, G., Makela, T. P. and Medema, R. H. (2000) p21 inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage checkpoint. J. Biol. Chem. 275, 30638-43.
Steinman, R. A., Hoffman, B., Iro, A., Guillouf, C., Liebermann, D. A. and el-Houseini, M. E. (1994) Induction of p21 (WAF-1/CIP1) during differentiation. Oncogene 9, 3389-96.
Steller, H. (1995) Mechanisms and genes of cellular suicide. Science 267, 1445-9.
Stevens, M. L. Fundamentals of clinical hematology. (1997)
Stommel, J. M., Marchenko, N. D., Jimenez, G. S., Moll, U. M., Hope, T. J. and Wahl, G. M. (1999) A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J. 18, 1660-72.
Strasser, A., O''Connor, L. and Dixit, V. M. (2000) Apoptosis signaling. Annu. Rev. Biochem. 69, 217-45.
Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., Larochette, N., Goodlett, D. R., Aebersold, R., Siderovski, D. P., Penninger, J. M. and Kroemer, G. (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397, 441-6.
Takao, N., Kato, H., Mori, R., Morrison, C., Sonada, E., Sun, X., Shimizu, H., Yoshioka, K., Takeda, S. and Yamamoto, K. (1999) Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation. Oncogene 18, 7002-9.
Tamir, A., Howard, J., Higgins, R. R., Li, Y. J., Berger, L., Zacksenhaus, E., Reis, M. and Ben-David, Y. (1999) Fli-1, an Ets-related transcription factor, regulates erythropoietin-induced erythroid proliferation and differentiation: evidence for direct transcriptional repression of the Rb gene during differentiation. Mol. Cell. Biol. 19, 4452-64.
Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y. and Nakamura, Y. (2000) A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404, 42-9.
Tanuma, N., Nakamura, K. and Kikuchi, K. (1999) Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase epsilon expression during macrophage differentiation. Eur. J. Biochem. 259, 46-54.
Tao, W. and Levine, A. J. (1999) Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53. Proc. Natl. Acad. Sci. USA 96, 3077-80.
Tassan, J. P., Schultz, S. J., Bartek, J. and Nigg, E. A. (1994) Cell cycle analysis of the activity, subcellular localization, and subunit composition of human CAK (CDK-activating kinase). J. Cell Biol. 127, 467-78.
Taylor, W. R. and Stark, G. R. (2001) Regulation of the G2/M transition by p53. Oncogene 20, 1803-15.
Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456-62.
Thornberry, N. A. and Lazebnik, Y. (1998) Caspases: enemies within. Science 281, 1312-6.
Thullberg, M., Bartkova, J., Khan, S., Hansen, K., Ronnstrand, L., Lukas, J., Strauss, M. and Bartek, J. (2000) Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors. FEBS Lett. 470, 161-6.
Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S. Y., Taya, Y., Prives, C. and Abraham, R. T. (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev. 13, 152-7.
Unger, T., Juven-Gershon, T., Moallem, E., Berger, M., Vogt Sionov, R., Lozano, G., Oren, M. and Haupt, Y. (1999) Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. EMBO J. 18, 1805-14.
Vander Heiden, M. G., Chandel, N. S., Williamson, E. K., Schumacker, P. T. and Thompson, C. B. (1997) Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 91, 627-37.
Vaux, D. L., Haecker, G. and Strasser, A. (1994) An evolutionary perspective on apoptosis. Cell 76, 777-9.
Venot, C., Maratrat, M., Dureuil, C., Conseiller, E., Bracco, L. and Debussche, L. (1998) The requirement for the p53 proline-rich functional domain for mediation of apoptosis is correlated with specific PIG3 gene transactivation and with transcriptional repression. EMBO J. 17, 4668-79.
Vogelstein, B., Lane, D. and Levine, A. J. (2000) Surfing the p53 network. Nature 408, 307-10.
Vousden, K. H. and Woude, G. F. (2000) The ins and outs of p53. Nat. Cell Biol. 2, E178-80.
Waga, S., Hannon, G. J., Beach, D. and Stillman, B. (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369, 574-8.
Walker, D. H. and Maller, J. L. (1991) Role for cyclin A in the dependence of mitosis on completion of DNA replication. Nature 354, 314-7.
Walker, K. K. and Levine, A. J. (1996) Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc .Natl. Acad. Sci. USA 93, 15335-40.
Wang, M. C., Liu, J. H. and Wang, F. F. (1997) Protein tyrosine phosphatase-dependent activation of beta-globin and delta-aminolevulinic acid synthase genes in the camptothecin-induced IW32 erythroleukemia cell differentiation. Mol. Pharmacol. 51, 558-66.
Wang, X. W., Forrester, K., Yeh, H., Feitelson, M. A., Gu, J. R. and Harris, C. C. (1994) Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proc. Natl. Acad. Sc. USA 91, 2230-4.
Wang, X. W., Yeh, H., Schaeffer, L., Roy, R., Moncollin, V., Egly, J. M., Wang, Z., Freidberg, E. C., Evans, M. K., Taffe, B. G. and et al. (1995) p53 modulation of TFIIH-associated nucleotide excision repair activity. Nat. Genet. 10, 188-95.
Wang, Y., Reed, M., Wang, P., Stenger, J. E., Mayr, G., Anderson, M. E., Schwedes, J. F. and Tegtmeyer, P. (1993) p53 domains: identification and characterization of two autonomous DNA-binding regions. Genes Dev. 7, 2575-86.
Watanabe, T., Kume, T. and Oishi, M. (1992) Alteration of phosphotyrosine-containing proteins at the early stage of erythroid differentiation of mouse erythroleukemia (MEL) cells. J. Biol. Chem. 267, 17116-20.
Waterman, M. J., Stavridi, E. S., Waterman, J. L. and Halazonetis, T. D. (1998) ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat. Genet. 19, 175-8.
Waterman, M. J., Stavridi, E. S., Waterman, J. L. and Halazonetis, T. D. (1998 ATM-dependent activation of p53 involves dephosphorylation and association with 14-3-3 proteins. Nat. Genet. 19, 175-8.
White, E. (1996) Life, death, and the pursuit of apoptosis. Genes Dev. 10, 1-15.
Wolter, K. G., Hsu, Y. T., Smith, C. L., Nechushtan, A., Xi, X. G. and Youle, R. J. (1997) Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139, 1281-92.
Wu, G. S., Burns, T. F., McDonald, E. R., 3rd, Jiang, W., Meng, R., Krantz, I. D., Kao, G., Gan, D. D., Zhou, J. Y., Muschel, R., Hamilton, S. R., Spinner, N. B., Markowitz, S., Wu, G. and el-Deiry, W. S. (1997) KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat. Genet. 17, 141-3.
Wyllie, A. (1998) Apoptosis. An endonuclease at last. Nature 391, 20-1.
Yaginuma, Y. and Westphal, H. (1992) Abnormal structure and expression of the p53 gene in human ovarian carcinoma cell lines. Cancer Res. 52, 4196-9.
Yang, J., Liu, X., Bhalla, K., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T. I., Jones, D. P. and Wang, X. (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129-32.
Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W. and Vogelstein, B. (2001) PUMA induces the rapid apoptosis of colorectal cancer cells. Mol. Cell 7, 673-82.
Zha, J., Harada, H., Yang, E., Jockel, J. and Korsmeyer, S. J. (1996) Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 87, 619-28.
Zhang, P., Liegeois, N. J., Wong, C., Finegold, M., Hou, H., Thompson, J. C., Silverman, A., Harper, J. W., DePinho, R. A. and Elledge, S. J. (1997) Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature 387, 151-8.
Zhang, P., Liegeois, N. J., Wong, C., Finegold, M., Hou, H., Thompson, J. C., Silverman, A., Harper, J. W., DePinho, R. A. and Elledge, S. J. (1997) Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature 387, 151-8.
Zhang, Y., Fujita, N. and Tsuruo, T. (1999) Caspase-mediated cleavage of p21Waf1/Cip1 converts cancer cells from growth arrest to undergoing apoptosis. Oncogene 18, 1131-8.
Zhou, B. B., Li, H., Yuan, J. and Kirschner, M. W. (1998) Caspase-dependent activation of cyclin-dependent kinases during Fas-induced apoptosis in Jurkat cells. Proc. Natl. Acad. Sci. USA 95, 6785-90.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top