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研究生:陳似蓉
研究生(外文):Szu-JungChen
論文名稱:紫外線以及凍傷造成的細胞凋亡需由 WOX1 參與
論文名稱(外文):Tumor suppressor WWOX/WOX1 is essential in UV irradiation/frostbite-induced membrane bubbling and death
指導教授:張南山
指導教授(外文):Nan-Shan Chang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:分子醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:67
中文關鍵詞:纖維母細胞COS7MEFWOX1TRAF2紫外線凍傷細胞凋亡
外文關鍵詞:FibroblastCOS7MEFWOX1TRAF2UVFrostbiteApoptosis
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當一個細胞受到紫外線照射,細胞在 30-60 分鐘開始進行一種不典型的細胞凋
亡。 根據觀察,紫外線的能量似乎被儲存在細胞核中,造成核蛋白質氧化並產生
氣體。這些氣體會導致核孔擴張,通透過細胞質,產生一個單一的大膜泡,我們定
義為 membrane bubbling。而且低溫會加速紫外線形成 membrane bubbling。不同於典型的細胞凋亡,進行 membrane bubbling 的細胞較少表現 DNA 斷裂片段化、
細胞核萎縮、細胞膜翻轉…⋯…⋯等現象。根據電子顯微鏡觀察,受到紫外線以及凍
傷的細胞表現出明顯的核孔擴張。腫瘤壞死因子-α受體相關因子 2 (TNF-α receptor-associated factor2,TRAF2) 短暫的過度表現在細胞中,有效地抑制了細胞
產生 membrane bubbling。TRAF2 蛋白能啟動 NFκB 的訊息傳遞路徑促進抗細胞
凋亡,且 TRAF2 蛋白豐富表現在正常皮膚組織。在凍傷皮膚組織,TRAF2 蛋白表
現量顯著下降,反而是 WOX1 蛋白的表現量大幅增加。長時間影像攝影分析觀察
發現,COS7 纖維母細胞受到紫外線以及凍傷刺激後,腫瘤抑制基因 p53 的 Ser46
和腫瘤抑制基因 WOX1 的 pY33 會被磷酸化。相較之下,在同樣的刺激情況下,
WWOX 基因剔除的小鼠胚胎纖維母細胞 (mouse embryonic fibroblasts, MEF)
membrane bubbling 的情況顯著降低。這些細胞不但缺乏 WOX1 的表現,而且幾
乎檢測不到 P53。此外, 暫時過量表達 dominant-negative p53 基因(S46G-p53)
顯著抑制 membrane bubbling,並顯著促進 WOX1 和 TRAF2 與 p53 蛋白分離。表
示 WOX1 和 p53 在促進 membrane bubbling 事件為關鍵影響因子。在作用機轉上,
經過紫外線以及凍傷影響後,在 30 分鐘內 WOX1 從 WOX1/TRAF2 複合物解離,
且釋放的 WOX1 結合 p53 轉移到細胞核,最後引起細胞死亡。結論,紫外線能量
被儲存在細胞核中,容易被轉化且經由氣泡的形式釋放,但是,WOX1/p53 如何控
制細胞核釋放能量還有待確定。

When a cell receives UV irradiation, an untypical apoptosis occurs rapidly in less than 30-60 min. The UV energy appears to be stored in the nucleus for oxidizing nuclear proteins and generating gases. These gases cause nuclear pore enlargement, drive through the cytoplasm, and produce a single large-size membrane bubble or a hot air balloon (hereby designated bubbling). Cold shock enhances the UV effect. Unlike typical apoptosis, no DNA fragmentation, nuclear condensation, membrane blebbing, and flip over of phosphatidylserine (PS) on cell membrane was observed. By electron microscopy, the nuclear pore size was increased in UV-exposed/frostbitten cells, compared to those of control cells. TRAF2 (TNF-α receptor-associated factor 2) is known to promote anti-apoptosis through the NFκB (Nuclear factor κB) signal pathway and is abundant in normal skin tissue. TRAF2 expression was significantly decreased in frostbitten skin tissues compared to normal skin tissues, whereas the expression of WOX1 (also known as WWOX or FOR) was greatly increased in frostbitten skin. Co-immunoprecipitation revealed that post UV irradiation/cold shock, p53 was phosphorylated at Ser46 and WOX1 was phosphorylated at Tyr33 in COS7 cells. This finding suggests that WOX1 and p53 play a crucial role in promoting the bubbling event. Mechanistically, UV/cold shock induced WOX1 release from the WOX1/TRAF2 complex in 30 minutes, and the released WOX1 bound p53 for relocating to the nucleus and causing cell death. Under similar condition, the level of bubbling of Wwox-/- MEF cells was significantly reduced. Since Wwox-/- MEF cells did not express WOX1 protein, these cells had barely detectable pS46-p53 protein expression. Moreover, transient overexpression of dominant-negative p53 (dn-p53 or S46G-p53) significantly inhibited membrane bubbling through promoting WOX1 dissociated from p53 and TRAF2. In conclusion, UV energy is stored in the nucleus, and can be readily transformed and released as a hot air balloon, which is WOX1/p53-dependent. How WOX1/p53 controls energy release from the nucleus remains to be established.
中文摘要.....................................................................................I
Abstract.....................................................................................II
誌謝...........................................................................................IV
Index of figures...................... ................................................VIII Abbreviation............................................................……............X Introduction...............................................................................1
Goals of this study..........................................……………………..1 Frostbite...................................................……………………........1
Skin Biology...................................................…………………......1
Programmed cell death................................................……........2
TNF induces programmed cell death.....................……...………..3
TRAF2 is essential in the inhibition of TNFα-induced cell death.........................................................………………………….4
WW domain-containing oxidoreductase WOX1......……………......6
Rationale..................................................................……….......14
Materials and Methods.............................................……..........15
Cell lines.....................................................................…….......15
Wwox Knockout Mice production.................................………...15
Chemicals and antibodies..........................................……….....15
DNA constructs.........................................................……........16 Electroporation.........................................................……….....16
Förster (Fluorescence) resonance energy transfer (FRET)................................................................................16 Immunofluorescence.........................................................17
Co-immunoprecipitation and immunoblotting...................18
Nuclear extraction.............................................................18 Immunohistochemistry......................................................19
Results..............................................................................20
Membrane bubbling - an untypical apoptosis feature........20
UV irradiation and cold shock induce membrane bubblin..20
Membrane bubbling is WOX1-dependent...........................20
TRAF2 significantly suppresses membrane bubbling.........21
WOX1 physically interacts with TRAF2............................22
WOX1 / p53 complex formation and translocation in the nucleoli causing membrane bubbling................................................23
Dominant-negative p53 inhibits membrane bubbling.........24
Discussion..................................................................................25
References..............................................................................28 Figures.......................................................................................44
1. Ikaheimo, T. M., and Hassi, J. (2011) Frostbites in circumpolar areas. Glob Health Action 4
2. Alibardi, L. (2003) Adaptation to the land: The skin of reptiles in comparison to that of amphibians and endotherm amniotes. J Exp Zool B Mol Dev Evol 298, 12-41
3. Breitkreutz, D., Mirancea, N., and Nischt, R. (2009) Basement membranes in skin: unique matrix structures with diverse functions? Histochem Cell Biol 132, 1-10
4. Rook's textbook of dermatology. Rook, A., and Burns, T. Blackwell Science, Malden, Mass. 4 v. (paged continuously)
5. Iozzo, R. V. (2005) Basement membrane proteoglycans: from cellar to ceiling. Nat Rev Mol Cell Biol 6, 646-656
6. The vertebrate body. Romer, A. S., and Parsons, T. S. Saunders, Philadelphia. viii, 624 p.
7. Kukhta, V. K., Marozkina, N. V., Sokolchik, I. G., and Bogaturova, E. V. (2003) Molecular mechanisms of apoptosis. Ukr Biokhim Zh 75, 5-9
8. Adrain, C., Slee, E. A., Harte, M. T., and Martin, S. J. (1999) Regulation of apoptotic protease activating factor-1 oligomerization and apoptosis by the WD-40 repeat region. J Biol Chem 274, 20855-20860
9. Edelmann, B., Bertsch, U., Tchikov, V., Winoto-Morbach, S., Perrotta, C., Jakob, M., Adam-Klages, S., Kabelitz, D., and Schutze, S. (2011) Caspase-8 and caspase-7 sequentially mediate proteolytic activation of acid sphingomyelinase in TNF-R1 receptosomes. EMBO J 30, 379-39410. Chandrasekar, B., Vemula, K., Surabhi, R. M., Li-Weber, M., Owen-Schaub, L. B., Jensen, L. E., and Mummidi, S. (2004) Activation of intrinsic and extrinsic proapoptotic signaling pathways in interleukin-18-mediated human cardiac endothelial cell death. J Biol Chem 279, 20221-20233
11. Grell, M., Zimmermann, G., Gottfried, E., Chen, C. M., Grunwald, U., Huang, D. C., Wu Lee, Y. H., Durkop, H., Engelmann, H., Scheurich, P., Wajant, H., and Strasser, A. (1999) Induction of cell death by tumour necrosis factor (TNF) receptor 2, CD40 and CD30: a role for TNF-R1 activation by endogenous membrane-anchored TNF. EMBO J 18, 3034-3043
12. Terry Powers, J. L., Mace, K. E., Parfrey, H., Lee, S. J., Zhang, G., and Riches, D. W. (2010) TNF receptor-1 (TNF-R1) ubiquitous scaffolding and signaling protein interacts with TNF-R1 and TRAF2 via an N-terminal docking interface. Biochemistry 49, 7821-7829
13. Hedrych-Ozimina, A., Behrendt, K., Hao, Z., Pofahl, R., Ussath, D., Knaup, R., Krieg, T., and Haase, I. (2010) Enhanced contact allergen- and UVB-induced keratinocyte apoptosis in the absence of CD95/Fas/Apo-1. Cell Death Differ 18, 155-163
14. Ramaswamy, M., Cleland, S. Y., Cruz, A. C., and Siegel, R. M. (2009) Many checkpoints on the road to cell death: regulation of Fas-FasL interactions and Fas signaling in peripheral immune responses. Results Probl Cell Differ 49, 17-47
15. Tabibzadeh, S., Zupi, E., Babaknia, A., Liu, R., Marconi, D., and Romanini, C.
(1995) Site and menstrual cycle-dependent expression of proteins of the tumour necrosis factor (TNF) receptor family, and BCL-2 oncoprotein and phase-specific production of TNF alpha in human endometrium. Hum Reprod 10, 277-286
16. Strasser, A., Jost, P. J., and Nagata, S. (2009) The many roles of FAS receptor signaling in the immune system. Immunity 30, 180-192
17. Nakayama, S., Semba, S., Maeda, N., Aqeilan, R. I., Huebner, K., and Yokozaki, H. (2008) Role of the WWOX gene, encompassing fragile region FRA16D, in suppression of pancreatic carcinoma cells. Cancer Sci 99, 1370-1376
18. Clohessy, J. G., Zhuang, J., de Boer, J., Gil-Gomez, G., and Brady, H. J. (2006) Mcl-1 interacts with truncated Bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis. J Biol Chem 281, 5750-5759
19. Cossarizza, A., Franceschi, C., Monti, D., Salvioli, S., Bellesia, E., Rivabene, R., Biondo, L., Rainaldi, G., Tinari, A., and Malorni, W. (1995) Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria. Exp Cell Res 220, 232-240
20. Aggarwal, B. B., Schwarz, L., Hogan, M. E., and Rando, R. F. (1996) Triple helix-forming oligodeoxyribonucleotides targeted to the human tumor necrosis factor (TNF) gene inhibit TNF production and block the TNF-dependent growth of human glioblastoma tumor cells. Cancer Res 56, 5156-5164
21. Green, D. R., and Reed, J. C. (1998) Mitochondria and apoptosis. Science 281, 1309-1312
22. Bernard, D., Quatannens, B., Vandenbunder, B., and Abbadie, C. (2001) Rel/NF-kappaB transcription factors protect against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by up-regulating the TRAIL decoy receptor DcR1. J Biol Chem 276, 27322-27328
23. Park, Y. C., Ye, H., Hsia, C., Segal, D., Rich, R. L., Liou, H. C., Myszka, D. G., and Wu, H. (2000) A novel mechanism of TRAF signaling revealed by
structural and functional analyses of the TRADD-TRAF2 interaction. Cell 101,
777-787
24. Ndebele, K., Gona, P., Jin, T. G., Benhaga, N., Chalah, A., Degli-Esposti, M.,
and Khosravi-Far, R. (2008) Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced mitochondrial pathway to apoptosis and caspase activation is potentiated by phospholipid scramblase-3. Apoptosis 13, 845-856
25. Li, L., Soetandyo, N., Wang, Q., and Ye, Y. (2009) The zinc finger protein A20 targets TRAF2 to the lysosomes for degradation. Biochim Biophys Acta 1793, 346-353
26. Arkan, M. C., and Greten, F. R. (2011) IKK- and NF-kappaB-mediated functions in carcinogenesis. Curr Top Microbiol Immunol 349, 159-169
27. Wei, W., Wang, D., Shi, J., Xiang, Y., Zhang, Y., Liu, S., Liu, Y., and Zheng, D.
(2010) Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces chemotactic migration of monocytes via a death receptor 4-mediated RhoGTPase pathway. Mol Immunol 47, 2475-2484
28. Xiao, G., and Fu, J. (2011) NF-kappaB and cancer: a paradigm of Yin-Yang. Am J Cancer Res 1, 192-221
29. Yu, C., Argyropoulos, G., Zhang, Y., Kastin, A. J., Hsuchou, H., and Pan, W.
(2008) Neuroinflammation activates Mdr1b efflux transport through NFkappaB: promoter analysis in BBB endothelia. Cell Physiol Biochem 22, 745-756
30. Bonizzi, G., and Karin, M. (2004) The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 25, 280-288
31. Bradley, J. R., and Pober, J. S. (2001) Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene 20, 6482-6491
32. Wajant, H., Henkler, F., and Scheurich, P. (2001) The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signal 13, 389-400
33. Hayden, M. S., and Ghosh, S. (2008) Shared principles in NF-kappaB signaling. Cell 132, 344-362
34. Baud, V., and Karin, M. (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11, 372-377
35. Yeh, W. C., Shahinian, A., Speiser, D., Kraunus, J., Billia, F., Wakeham, A., de la Pompa, J. L., Ferrick, D., Hum, B., Iscove, N., Ohashi, P., Rothe, M., Goeddel, D. V., and Mak, T. W. (1997) Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity 7, 715-725
36. Tada, K., Okazaki, T., Sakon, S., Kobarai, T., Kurosawa, K., Yamaoka, S., Hashimoto, H., Mak, T. W., Yagita, H., Okumura, K., Yeh, W. C., and Nakano, H. (2001) Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. J Biol Chem 276, 36530-36534
37. Grech, A. P., Amesbury, M., Chan, T., Gardam, S., Basten, A., and Brink, R.
(2004) TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells. Immunity 21, 629-642
38. Zhang, L., Blackwell, K., Thomas, G. S., Sun, S., Yeh, W. C., and Habelhah, H. (2009) TRAF2 suppresses basal IKK activity in resting cells and TNFalpha can activate IKK in TRAF2 and TRAF5 double knockout cells. J Mol Biol 389, 495-510
39. Zhang, L., Blackwell, K., Shi, Z., and Habelhah, H. (2010) The RING domain of TRAF2 plays an essential role in the inhibition of TNFalpha-induced cell death but not in the activation of NF-kappaB. J Mol Biol 396, 528-539
40. Chang, N. S., Pratt, N., Heath, J., Schultz, L., Sleve, D., Carey, G. B., and Zevotek, N. (2001) Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity. J Biol Chem 276, 3361-3370
41. Aqeilan, R. I., Donati, V., Gaudio, E., Nicoloso, M. S., Sundvall, M., Korhonen, A., Lundin, J., Isola, J., Sudol, M., Joensuu, H., Croce, C. M., and Elenius, K.
(2007) Association of Wwox with ErbB4 in breast cancer. Cancer Res 67, 9330-9336
42. Aqeilan, R. I., Hagan, J. P., Aqeilan, H. A., Pichiorri, F., Fong, L. Y., and Croce, C. M. (2007) Inactivation of the Wwox gene accelerates forestomach tumor progression in vivo. Cancer Res 67, 5606-5610
43. Chang, N. S., Hsu, L. J., Lin, Y. S., Lai, F. J., and Sheu, H. M. (2007) WW domain-containing oxidoreductase: a candidate tumor suppressor. Trends Mol Med 13, 12-22
44. Bednarek, A. K., Keck-Waggoner, C. L., Daniel, R. L., Laflin, K. J., Bergsagel, P. L., Kiguchi, K., Brenner, A. J., and Aldaz, C. M. (2001) WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. Cancer Res 61, 8068-8073
45. Bednarek, A. K., Laflin, K. J., Daniel, R. L., Liao, Q., Hawkins, K. A., and Aldaz, C. M. (2000) WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer. Cancer Res 60, 2140-2145
46. O'Keefe, L. V., Colella, A., Dayan, S., Chen, Q., Choo, A., Jacob, R., Price, G., Venter, D., and Richards, R. I. (2011) Drosophila orthologue of WWOX, the chromosomal fragile site FRA16D tumour suppressor gene, functions in aerobic metabolism and regulates reactive oxygen species. Hum Mol Genet 20, 497-509
47. Ried, K., Finnis, M., Hobson, L., Mangelsdorf, M., Dayan, S., Nancarrow, J. K., Woollatt, E., Kremmidiotis, G., Gardner, A., Venter, D., Baker, E., and Richards, R. I. (2000) Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. Hum Mol Genet 9, 1651-1663
48. Watanabe, A., Hippo, Y., Taniguchi, H., Iwanari, H., Yashiro, M., Hirakawa, K., Kodama, T., and Aburatani, H. (2003) An opposing view on WWOX protein function as a tumor suppressor. Cancer Res 63, 8629-8633
49. Hong, Q., Hsu, L. J., Schultz, L., Pratt, N., Mattison, J., and Chang, N. S. (2007) Zfra affects TNF-mediated cell death by interacting with death domain protein TRADD and negatively regulates the activation of NF-kappaB, JNK1, p53 and WOX1 during stress response. BMC Mol Biol 8, 50
50. Hsu, L. J., Hong, Q., Schultz, L., Kuo, E., Lin, S. R., Lee, M. H., Lin, Y. S., and Chang, N. S. (2008) Zfra is an inhibitor of Bcl-2 expression and cytochrome c release from the mitochondria. Cell Signal 20, 1303-1312
51. Aqeilan, R. I., Palamarchuk, A., Weigel, R. J., Herrero, J. J., Pekarsky, Y., and Croce, C. M. (2004) Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. Cancer Res 64, 8256-8261
52. Aqeilan, R. I., Pekarsky, Y., Herrero, J. J., Palamarchuk, A., Letofsky, J., Druck, T., Trapasso, F., Han, S. Y., Melino, G., Huebner, K., and Croce, C. M. (2004)Functional association between Wwox tumor suppressor protein and p73, a
p53 homolog. Proc Natl Acad Sci U S A 101, 4401-4406
53. Gaudio, E., Palamarchuk, A., Palumbo, T., Trapasso, F., Pekarsky, Y., Croce,
C. M., and Aqeilan, R. I. (2006) Physical association with WWOX suppresses
c-Jun transcriptional activity. Cancer Res 66, 11585-11589
54. Einbond, A., and Sudol, M. (1996) Towards prediction of cognate complexes
between the WW domain and proline-rich ligands. FEBS Lett 384, 1-8
55. McDonald, C. B., Buffa, L., Bar-Mag, T., Salah, Z., Bhat, V., Mikles, D. C.,
Deegan, B. J., Seldeen, K. L., Malhotra, A., Sudol, M., Aqeilan, R. I., Nawaz, Z., and Farooq, A. (2012) Biophysical Basis of the Binding of WWOX Tumor Suppressor to WBP1 and WBP2 Adaptors. J Mol Biol (article in press)
56. Aqeilan, R. I., Trapasso, F., Hussain, S., Costinean, S., Marshall, D., Pekarsky, Y., Hagan, J. P., Zanesi, N., Kaou, M., Stein, G. S., Lian, J. B., and Croce, C. M. (2007) Targeted deletion of Wwox reveals a tumor suppressor function. Proc Natl Acad Sci U S A 104, 3949-3954
57. Aqeilan, R. I., Hassan, M. Q., de Bruin, A., Hagan, J. P., Volinia, S., Palumbo, T., Hussain, S., Lee, S. H., Gaur, T., Stein, G. S., Lian, J. B., and Croce, C. M.
(2008) The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism. J Biol Chem 283, 21629-21639
58. Ludes-Meyers, J. H., Kil, H., Nunez, M. I., Conti, C. J., Parker-Thornburg, J., Bedford, M. T., and Aldaz, C. M. (2007) WWOX hypomorphic mice display a higher incidence of B-cell lymphomas and develop testicular atrophy. Genes Chromosomes Cancer 46, 1129-1136
59. Paige, A. J., Taylor, K. J., Taylor, C., Hillier, S. G., Farrington, S., Scott, D., Porteous, D. J., Smyth, J. F., Gabra, H., and Watson, J. E. (2001) WWOX: acandidate tumor suppressor gene involved in multiple tumor types. Proc Natl
Acad Sci U S A 98, 11417-11422
60. Aqeilan, R. I., Kuroki, T., Pekarsky, Y., Albagha, O., Trapasso, F., Baffa, R.,
Huebner, K., Edmonds, P., and Croce, C. M. (2004) Loss of WWOX
expression in gastric carcinoma. Clin Cancer Res 10, 3053-3058
61. Ramos, D., Abba, M., Lopez-Guerrero, J. A., Rubio, J., Solsona, E., Almenar,
S., Llombart-Bosch, A., and Aldaz, C. M. (2008) Low levels of WWOX protein immunoexpression correlate with tumour grade and a less favourable outcome in patients with urinary bladder tumours. Histopathology 52, 831-839
62. Wang, M., Gu, J., Wang, Y., and Gong, B. (2009) Loss of WWOX expression in human extrahepatic cholangiocarcinoma. J Cancer Res Clin Oncol 135, 39-44
63. Salah, Z., Aqeilan, R., and Huebner, K. (2010) WWOX gene and gene product: tumor suppression through specific protein interactions. Future Oncol 6, 249-259
64. Lai, F. J., Cheng, C. L., Chen, S. T., Wu, C. H., Hsu, L. J., Lee, J. Y., Chao, S. C., Sheen, M. C., Shen, C. L., Chang, N. S., and Sheu, H. M. (2005) WOX1 is essential for UVB irradiation-induced apoptosis and down-regulated via translational blockade in UVB-induced cutaneous squamous cell carcinoma in vivo. Clin Cancer Res 11, 5769-5777
65. Fabbri, M., Iliopoulos, D., Trapasso, F., Aqeilan, R. I., Cimmino, A., Zanesi, N., Yendamuri, S., Han, S. Y., Amadori, D., Huebner, K., and Croce, C. M. (2005) WWOX gene restoration prevents lung cancer growth in vitro and in vivo. Proc Natl Acad Sci U S A 102, 15611-15616
66. Qin, H. R., Iliopoulos, D., Semba, S., Fabbri, M., Druck, T., Volinia, S., Croce, C. M., Morrison, C. D., Klein, R. D., and Huebner, K. (2006) A role for the WWOX gene in prostate cancer. Cancer Res 66, 6477-6481
67. Chang, Y. C., Chiu, Y. F., Liu, P. H., Shih, K. C., Lin, M. W., Sheu, W. H., Quertermous, T., Curb, J. D., Hsiung, C. A., Lee, W. J., Lee, P. C., Chen, Y. T., and Chuang, L. M. (2012) Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort. Clin Endocrinol (Oxf) 76, 365-372
68. Chang, L., Jones, Y., Ellisman, M. H., Goldstein, L. S., and Karin, M. (2003) JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev Cell 4, 521-533
69. Chang, N. S., Doherty, J., and Ensign, A. (2003) JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J Biol Chem 278, 9195-9202
70. Chang, N. S., Doherty, J., Ensign, A., Lewis, J., Heath, J., Schultz, L., Chen, S. T., and Oppermann, U. (2003) Molecular mechanisms underlying WOX1 activation during apoptotic and stress responses. Biochem Pharmacol 66, 1347-1354
71. Chang, N. S., Doherty, J., Ensign, A., Schultz, L., Hsu, L. J., and Hong, Q.
(2005) WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. J Biol Chem 280, 43100-43108
72. Chang, N. S., Schultz, L., Hsu, L. J., Lewis, J., Su, M., and Sze, C. I. (2005) 17beta-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo. Oncogene 24, 714-723
73. Sex Hormones. Su, W. P., Chen, S. H., Chen, S. J., Chou, P. Y., Huang, C. C., and Chang, N. S. InTech, Janeza Trdine 9, 51000 Rijeka, Croatia. 19
74. Cooper, N. R. (1985) The classical complement pathway: activation and regulation of the first complement component. Adv Immunol 37, 151-216
75. Schumaker, V. N., Zavodszky, P., and Poon, P. H. (1987) Activation of the first component of complement. Annu Rev Immunol 5, 21-42
76. Arlaud, G. J., Gaboriaud, C., Thielens, N. M., Rossi, V., Bersch, B., Hernandez, J. F., and Fontecilla-Camps, J. C. (2001) Structural biology of C1: dissection of a complex molecular machinery. Immunol Rev 180, 136-145
77. Calcott, M. A., and Muller-Eberhard, H. J. (1972) C1q protein of human complement. Biochemistry 11, 3443-3450
78. Reid, K. B., and Thompson, R. A. (1983) Characterization of a non-functional form of C1q found in patients with a genetically linked deficiency of C1q activity. Mol Immunol 20, 1117-1125
79. Reid, K. B. (1989) Chemistry and molecular genetics of C1q. Behring Inst Mitt, 8-19
80. Kojouharova, M. S., Tsacheva, I. G., Tchorbadjieva, M. I., Reid, K. B., and Kishore, U. (2003) Localization of ligand-binding sites on human C1q globular head region using recombinant globular head fragments and single-chain antibodies. Biochim Biophys Acta 1652, 64-74
81. Ghai, R., Waters, P., Roumenina, L. T., Gadjeva, M., Kojouharova, M. S., Reid, K. B., Sim, R. B., and Kishore, U. (2007) C1q and its growing family. Immunobiology 212, 253-266
82. Gadjeva, M. G., Rouseva, M. M., Zlatarova, A. S., Reid, K. B., Kishore, U., and
Kojouharova, M. S. (2008) Interaction of human C1q with IgG and IgM:
revisited. Biochemistry 47, 13093-13102
83. Paidassi, H., Tacnet-Delorme, P., Garlatti, V., Darnault, C., Ghebrehiwet, B., Gaboriaud, C., Arlaud, G. J., and Frachet, P. (2008) C1q binds phosphatidylserine and likely acts as a multiligand-bridging molecule in apoptotic cell recognition. J Immunol 180, 2329-2338
84. Hosszu, K. K., Santiago-Schwarz, F., Peerschke, E. I., and Ghebrehiwet, B.
(2010) Evidence that a C1q/C1qR system regulates monocyte-derived dendritic cell differentiation at the interface of innate and acquired immunity. Innate Immun 16, 115-127
85. Calreticulin. Eggleton, P., and Michalak, M. Landes Bioscience/Eurekah.com ; Kluwer Academic/Plenum, Georgetown, Tex.New York, N.Y. 282 p.
86. Ghebrehiwet, B., and Peerschke, E. I. (2004) cC1q-R (calreticulin) and gC1q-R/p33: ubiquitously expressed multi-ligand binding cellular proteins involved in inflammation and infection. Mol Immunol 41, 173-183
87. Hong, Q., Sze, C. I., Lin, S. R., Lee, M. H., He, R. Y., Schultz, L., Chang, J. Y., Chen, S. J., Boackle, R. J., Hsu, L. J., and Chang, N. S. (2009) Complement C1q activates tumor suppressor WWOX to induce apoptosis in prostate cancer cells. PLoS One 4, e5755
88. Shapiro, L., and Scherer, P. E. (1998) The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol 8, 335-338
89. Suzuki, H., Takenaka, M., and Suzuki, K. (2007) Phenotypic characterization of spontaneously mutated rats showing lethal dwarfism and epilepsy. Comp Med 57, 360-369
90. Takenaka, M., Yagi, M., Amakasu, K., Suzuki, K., and Suzuki, H. (2008) Retarded differentiation of Leydig cells and increased apoptosis of germ cellsin the initial round of spermatogenesis of rats with lethal dwarf and epilepsy
(lde/lde) phenotypes. J Androl 29, 669-678
91. Sze, C. I., Su, M., Pugazhenthi, S., Jambal, P., Hsu, L. J., Heath, J., Schultz, L.,
and Chang, N. S. (2004) Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease. J Biol Chem 279, 30498-30506
92. Suzuki, H., Katayama, K., Takenaka, M., Amakasu, K., Saito, K., and Suzuki, K. (2009) A spontaneous mutation of the Wwox gene and audiogenic seizures in rats with lethal dwarfism and epilepsy. Genes Brain Behav 8, 650-660
93. O'Donnell, M. A., Legarda-Addison, D., Skountzos, P., Yeh, W. C., and Ting, A. T. (2007) Ubiquitination of RIP1 regulates an NF-kappaB-independent cell-death switch in TNF signaling. Curr Biol 17, 418-424
94. Tinel, A., Janssens, S., Lippens, S., Cuenin, S., Logette, E., Jaccard, B., Quadroni, M., and Tschopp, J. (2007) Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-kappaB pathway. EMBO J 26, 197-208
95. Chang, N. S. (2002) A potential role of p53 and WOX1 in mitochondrial apoptosis (review). Int J Mol Med 9, 19-24
96. Del Mare, S., Salah, Z., and Aqeilan, R. I. (2009) WWOX: its genomics, partners, and functions. J Cell Biochem 108, 737-745
97. Chang, J. Y., He, R. Y., Lin, H. P., Hsu, L. J., Lai, F. J., Hong, Q., Chen, S. J., and Chang, N. S. (2010) Signaling from membrane receptors to tumor suppressor WW domain-containing oxidoreductase. Exp Biol Med (Maywood) 235, 796-804
98. Kang, C. D., Lee, B. K., Kim, K. W., Kim, C. M., Kim, S. H., and Chung, B. S. (1996) Signaling mechanism of PMA-induced differentiation of K562 cells. Biochem Biophys Res Commun 221, 95-100
99. Westberg, J. A., Zhang, K. Z., and Andersson, L. C. (1999) Regulation of neural differentiation by normal and mutant (G654A, amyloidogenic) gelsolin. FASEB J 13, 1621-1626
100. Lai, J. M., Wu, S., Huang, D. Y., and Chang, Z. F. (2002) Cytosolic retention of phosphorylated extracellular signal-regulated kinase and a Rho-associated kinase-mediated signal impair expression of p21(Cip1/Waf1) in phorbol 12-myristate-13- acetate-induced apoptotic cells. Mol Cell Biol 22, 7581-7592
101. Lin, H. P., Chang, J. Y., Lin, S. R., Lee, M. H., Huang, S. S., Hsu, L. J., and Chang, N. S. (2011) Identification of an In Vivo MEK/WOX1 Complex as a Master Switch for Apoptosis in T Cell Leukemia. Genes Cancer 2, 550-562
102. Lee, M. H., Lin, S. R., Chang, J. Y., Schultz, L., Heath, J., Hsu, L. J., Kuo, Y. M., Hong, Q., Chiang, M. F., Gong, C. X., Sze, C. I., and Chang, N. S. (2010) TGF-beta induces TIAF1 self-aggregation via type II receptor-independent signaling that leads to generation of amyloid beta plaques in Alzheimer's disease. Cell Death Dis 1, e110
103. Gwynn, B., Smith, R. S., Rowe, L. B., Taylor, B. A., and Peters, L. L. (2006) A mouse TRAPP-related protein is involved in pigmentation. Genomics 88, 196-203
104. Sacher, M., Kim, Y. G., Lavie, A., Oh, B. H., and Segev, N. (2008) The TRAPP complex: insights into its architecture and function. Traffic 9, 2032-2042
105. Wang, H. Y., Juo, L. I., Lin, Y. T., Hsiao, M., Lin, J. T., Tsai, C. H., Tzeng, Y. H., Chuang, Y. C., Chang, N. S., Yang, C. N., and Lu, P. J. (2012) WWdomain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3beta. Cell Death Differ 19, 1049-1059
106. Ferguson, B. W., Gao, X., Kil, H., Lee, J., Benavides, F., Abba, M. C., and Aldaz, C. M. (2012) Conditional Wwox deletion in mouse mammary gland by means of two Cre recombinase approaches. PLoS One 7, e36618
107. Roarty, K., and Serra, R. (2007) Wnt5a is required for proper mammary gland development and TGF-beta-mediated inhibition of ductal growth. Development 134, 3929-3939
108. Chapman, R. S., Lourenco, P. C., Tonner, E., Flint, D. J., Selbert, S., Takeda, K., Akira, S., Clarke, A. R., and Watson, C. J. (1999) Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev 13, 2604-2616
109. Katoh, M. (2007) STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer (Review). Int J Mol Med 19, 273-278
110. Mikels, A. J., and Nusse, R. (2006) Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol 4, e115
111. Kataoka, K., Shioda, S., Ando, K., Sakagami, K., Handa, H., and Yasuda, K.
(2004) Differentially expressed Maf family transcription factors, c-Maf and MafA, activate glucagon and insulin gene expression in pancreatic islet alpha- and beta-cells. J Mol Endocrinol 32, 9-20
112. Kataoka, K., Han, S. I., Shioda, S., Hirai, M., Nishizawa, M., and Handa, H.
(2002) MafA is a glucose-regulated and pancreatic beta-cell-specific
transcriptional activator for the insulin gene. J Biol Chem 277, 49903-49910
113. Rulifson, I. C., Karnik, S. K., Heiser, P. W., ten Berge, D., Chen, H., Gu, X., Taketo, M. M., Nusse, R., Hebrok, M., and Kim, S. K. (2007) Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci U S A 104, 6247-6252
114. Bouteille, N., Driouch, K., Hage, P. E., Sin, S., Formstecher, E., Camonis, J., Lidereau, R., and Lallemand, F. (2009) Inhibition of the Wnt/beta-catenin pathway by the WWOX tumor suppressor protein. Oncogene 28, 2569-2580

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