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研究生:蕭積晏
研究生(外文):Chi-Yan Hsiao
論文名稱:精氨酸甲基化酵素-6與林巴促進因子結合以增強基因活化之研究
論文名稱(外文):PRMT6 associates with LEF1 to enhance LEF1/beta-catenin transcriptional activity
指導教授:林陽生
學位類別:碩士
校院名稱:國立臺灣大學
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:2004
畢業學年度:93
語文別:英文
論文頁數:40
中文關鍵詞:精氨酸甲基化酵素
外文關鍵詞:LEF-1PRMT6
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Wnt訊息傳遞調控發育過程, 而該訊息的失控將會導致癌症的發生。Wnt分子藉由LEFs/beta-catenin來達成訊號傳遞的結果。在Wnt訊號的刺激下,beta-catenin累積在細胞質中並進入到細胞核內與LEFs結合活化特定基因。已知一些蛋白質會與beta-catenin/LEFs結合並增加或抑制beta-catenin/LEFs對於基因活化的能力。為了要尋找其他會影響beta-catenin/LEFs活化基因能力的蛋白質,我們利用LEFs家族中的兩個蛋白質LEF在酵母菌雙雜交法中當作餌在胚胎腦細胞基因庫與乳腺細胞基因庫中尋找會與LEF1或作用的蛋白質。最後找到了PRMT6,並利用GST拉下法及免疫沉澱法證明PRMT6的確會與LEF1作用。也以轉錄報導基因證實PRMT6會增進beta-catenin/LEF1活化基因的能力。
Wnt signals control developmental processes and its deregulation leads to various cancers. Wnt molecules transduce signals through beta-catenin/LEFs(LEF1, TCF4 and its homologs). Upon wnt signaling, beta-catenin accumulates and associates with LEFs to transactivate specific genes. LEFs are required for body plan formation, cell fate determination, cells proliferation and survival. It was well known that various proteins, such as CBP, HDAC, PIAS, and Groucho-related proteins, participated in LEFs/beta-catenin transcriptional activity. Here, we performed yeast two-hybrid screening through fetal brain libraray and mammary gland library to search additional proteins involved in LEFs/beta-catenin transcriptional activity. PRMT6 was identified to interact with LEF1 both in vivo and in vitro. It was also shown to enhance LEF1/beta-catenin transcriptional activity on reporter assay.
Abstract……………………………………………………………1
中文摘要……………………………………………………………2
Introduction………………………………………………………3
Materials and Methods…………………………………………11
Results……………………………………………………………16
Discussion………………………………………………………21
References………………………………………………………24
Tables……………………………………………………………29
Figures…………………………………………………………31
Adam Frankel, Neelu Yadav, Jaeho Lee, Tina L. Branscombe, Steven Clarke, and Mark T. Bedford. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. (2002) J. Biol Chem. 277, 3537-3543.

Barker N., Hurlstone A., Musisi H., Miles A., Bienz M., Clevers H. The chromatin remodeling factor Brg-1 interacts with beta-catenin to promote target gene activation. (2001) EMBO J. 17, 1935-4943.

Bedford, M.T., Frankel, A., Yaffe, M.B., Clarke, S., Leder, P. and Richard, S. Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains. (2000) J. Biol. Chem. 275, 16030–16036.

Bienz, M. and Clevers, H. Linking colorectal cancer to Wnt signaling. (2000) Cell 103, 311-320.

Brown, S., McGrath, M. J., Ooms, L. M., Gurung, R., Maimone, M. M., and Mitchell, C. A. Characterization of Two Isoforms of the Skeletal Muscle LIM Protein1, SLIM1.
(1999) J. Biol. Chem. 274, 27083–27091.

Bruhn,L. ,Munnerlyn,A. and Grosschedl,R. ALY, a context-dependent coactivator of lef1 and aml1,is required for TCR enhancer function. (1997) Genes & Dev. 11, 640-653.

Cadigan, K.M. and Nusse, R. Wnt signaling: A common theme in animal development. (1997) Genes & Dev. 11, 3286-3305.
Chen D., Ma, H., Hong, H., Koh, S.S., Huang, S.M., Schurter, B.T., Aswad, D.W. and Stallcup, M.R. Regulation of transcription by a protein methyltransferase (1999) Science 284, 2174–2177.
Chu, K., Niu, X., and Williams, L. T. A Fas-Associated Protein Factor, FAF1, Potentiates Fas-Mediated Apoptosis. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 11894–11898

Chung, C.D., Liao, J., Liu, B., Rao, X., Jay, P, Berta, P., and Shuai, K. Specific inhibition of Stat3 signal transduction by PIAS3. (1997) Science 278, 1803-1805.

Eastman, Q. and Grosschedl, R. Regulation of LEF-1/TCF transcription factors by Wnt and other signals. (1999) Curr. Opin. Cell Biol. 11, 233-240.

Fimia, G. M., De Cesare, D., and Sassone-Corsi, P. A Family of LIM-Only Transcriptional Coactivators: Tissue-Specific Expression and Selective Activation of CREB and CREM. (2000) Mol. Cell. Biol. 20, 8613–8622.

Funayama N., Fagotto F., McCrea P., Gumbiner B. M., Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. (1995) J. Cell. Biol. 128, 959-968.

Giese, K. and Grosschedl, R. LEF-1 contains an activation domain that stimulates transcription only in a specific context of factor binding sites. (1993) EMBO J. 19, 4667-4676.

Giese, K., Kingsley, C., Kirshner, J.R., and Grosschedl, R. Assembly and function of a TCR enhancer complex is dependent on LEF-1-induced DNA bending and multiple protein-protein interactions. (1995) Genes & Dev. 9, 995-1008.

Gross, M., Liu, B., Tan, J., French, F.S., Carey, M., and Shuai, K. Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells. (2001) Oncogene 20, 3880-3887.

Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., McCrea, P., Kintner, C., Noro, C.Y., Wylie, C. Overexpression of acdherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus. (1994) Cell. 79, 791-803.

Hsu, S-C., Galceran, J., and Grosschedl, R. Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with -catenin. (1998) Mol. Cell. Biol. 18, 4807-4818.

Kowenz-Leutz E and Leutz A. A C/EBP isoform recruits the SWI/SNF complex to activate myeloid genes. (1999) Mol Cell, 4, 735–743.



Lin W.J., Gary, J.D., Yang, M.C., Clarke, S. and Herschman, H.R. The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase. (1996) J. Biol. Chem. 271, 15034–15044.

Loughna, P. T., Mason, P., Bayol, S., and Brownson, C. The LIM-domain protein FHL1 (SLIM 1) exhibits functional regulation in skeletal muscle. (2000) Mol. Cell. Biol. Res. Commun. 3, 136–140.

Mariann,B. and Hans,C. Linking colorectal cancer to Wnt signaling. (2000) Cell, 103, 311-320.

Martin, B., Schneider, R., Janetzky, S., Waibler, Z., Pandur, P., Kuhl, M., Behrens, J., von der Mark, K., Starzinski-Powitz, A., and Wixler, V. The LIM-only protein FHL2 interacts with ß-catenin and promotes differentiation of mouse myoblasts. (2002) J. Cell Biol. 159, 113–122.

Molenaar, M., van de Wetering, M., Oosterwegel, M., Peterson, M. J., Godsave, S., Korinek, V., Roose, J., Destree, O., Clevers, H., XTCF3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. (1996) Cell. 86, 391-399.

Morgan, M. J., and Madgwick, A. J. Slim defines a novel family of LIM-proteins expressed in skeletal muscle. (1996) Biochem. Biophys. Res. Commun. 225, 632–638.

Mowen K.A., Tang, J., Zhu, W., Schurter, B.T., Shuai, K., Herschman, H.R. and David, M. Arginine Methylation of STAT1 Modulates IFN / -Induced Transcription. (2001) Cell 104, 731–741

Muchardt C and Yaniv M. A human homologue of Saccharomyces cerevisiae SNF2/SWI2 and Drosophila brm genes potentiates transcriptional activation by the glucocorticoid receptor. (1993) EMBO J, 12, 4279–4290.

Muller, J. M., Isele, U., Metzger, E., Rempel, A., Moser, M., Pscherer, A., Breyer, T.,
Holubarsch, C., Buettner, R., and Schule, R. The transcriptional coactivator FHL2 transmits Rho signals from the cell membrane into the nucleus. (2000) EMBO J. 19, 359–369.


Nishita,M., Hashimoto,M.K., Ogata,S., Laurent,M.N., Ueno,N., Shibuya,H. and Cho,K.W. Interaction between Wnt and TGF-β signalling pathways during formation of Spemann’s organizer. (2000) Nature, 403, 781-785.

Ostlund Farrants AK, Blomquist P, Kwon H and Wrange O. Glucocorticoid receptor–glucocorticoid response element binding stimulates nucleosome disruption by the SWI/SNF complex. (1997) Mol Cell Biol, 17, 895–905.

Pollack B.P., Kotenko, S.V., He, W., Izotova, L.S., Barnoski, B.L. and Pestka, S. The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity. (1999) J. Biol. Chem. 274, 31531–31542.
Ryu, S. W., and Kim, E. Apoptosis Induced by Human Fas-Associated Factor 1, hFAF1, Requires Its Ubiquitin Homologous Domain, but Not the Fas-Binding Domain. (2001) Biochem. Biophys. Res. Commun. 286, 1027–1032.

Ryu, S. W., Kim, E. Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex. (2003) J. Biol. Chem. 278, 24003-24010.

Sachdev, S., Bruhn, L., Sieber, H., Pichler, A., Melchior, F., and Frosschedl, R. PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nucear bodies. (2001) Genes & Dev. 15, 3088-3103.

Sampsom, E. M., Haque, Z. K., Ku, M. C., Tevosian, S. G., Albanese, C., Pestell, R. G., Paulson, K. E., and Yee, A. S. Negative regulation of the Wnt-beta-catenin pathway by the transcriptional repressor HBP1. (2001) EMBO. 20, 4500-4511.

Valentini S.R., Weiss, V.H. and Silver, P.A. Arginine methylation and binding of Hrp1p to the efficiency element for mRNA 3''-end formation. (1999) RNA 5, 272–280.

Wang W et al. Purification and biochemical heterogeneity of the mammalian SWI–SNF complex. (1996a) EMBO J, 15, 5370–5382.

Wang W, Xue Y, Zhou S, Kuo A, Cairns BR and Crabtree GR. Diversity and specialization of mammalian SWI/SNF complexes. (1996b) Genes & Dev, 10, 2117-2130.


Waterman M. L., Fisher W. H., and Jones K. A. A thymus-specific member of the HMG protein family regulates the human T cell receptor C enhancer. (1991) Genes & Dev. 5, 656-669.

Winston F., Allis C. D. The bromodomain: a chromatin targeting module? (1999) Nat. Struct. Biol. 7, 601-604.

Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. (1998) Annu. Rev. Cell Dev. Biol. 14, 59-88.

Xue Y, Canman JC, Lee CS, Nie Z, Yang D, Moreno GT, Young MK, Salmon ED and Wang W. The human SWI/SNF-B chromatin-remodelling complex is related to yeast Rsc and localizes at kinetochores of mitotic chromosomes. (2000) Proc Natl Acad Sci USA, 97, 13015–13020.
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