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第388回TSMMセミナー

2013/12/05

演題:Epigenetic Control of Chromatin-Dependent Transcription – Lessons from p53, AP-1, Brd4 and HPV

演者*:*Cheng-Ming Chiang, PhD

Professor of Biochemistry and Pharmacology

Simmons Comprehensive Cancer Center

University of Texas Southwestern Medical Center, U.S.A.

日時:2013年12月5日(木)17:00-18:30

会場:イノベーション棟8階講堂GooglrMap版へ(This seminar will be held in English)

要旨:Transcription in higher eukaryotes is controlled by an array of transcription factors, including the general transcription machinery, general cofactors, and gene-specific activators and repressors. The complexity of gene regulation is further conferred by the existence of multiple protein family members recognizing consensus or non-canonical DNA-binding sequences. The chromatin structure in the human genome and posttranslational modification on protein molecules provide an additional level of control in modulating gene activity. In this lecture, I will review these control mechanisms using human papillomavirus (HPV) E6 and E2 proteins as examples to illustrate how DNA tumor virus-encoded transcriptional regulators are able to reprogram cellular activities by targeting p53 tumor suppressor protein and activator protein-1 (AP-1), respectively, via recruitment of distinct coregulators, such as p300 histone acetyltransferase and the chromatin adaptor bromodomain-containing protein 4 (Brd4). The interplay among these viral and cellular proteins and the crosstalk between different posttranslational modifications regulate gene activity in response to various environmental stresses.

参考文献

1.Thomas, M.C. and C.-M. Chiang. (2005) E6 oncoprotein represses p53-dependent gene activation via inhibition of protein acetylation independently of inducing p53 degradation.

*/Mol. Cell/*17: 251-264.

2.Wu, S.-Y., A.Y. Lee, S.Y. Hou, J.K. Kemper, H. Erdjument-Bromage, P.
Tempst, and C.-M. Chiang. (2006) Brd4 links chromatin targeting to HPV transcriptional silencing.

*/Genes Dev/**.*20: 2383-2396.

3.Wu, S.-Y., A-Y. Lee, H.-T. Lai, H. Zhang, and C.-M. Chiang. 2013.
Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting.

*/Mol. Cell/*49: 843-857.

連絡先:筑波大学医学医療系 久武 幸司
Tel: 内線3929、 E-mail:kojihisa#@#md.tsukuba.ac.jp (#@#を@に置き換えて下さい。)

【筑波分子医学協会(TSMM)主催】HP http://www.md.tsukuba.ac.jp/public/tsmm/

TSMMセミナー担当  筑波大学医学医療系 船越祐司

*TSMMセミナーは、フロンティア医科学専攻(修士) 「医科学セミナーII」(担当:久武 幸司)、生命システム医学専攻&疾患制御医学専攻(博士)「最先端医学研究セミナー」(担当:熊谷 嘉人、武川 寛樹)及び「医学セミナー」(担当:専攻各教員)の関連セミナーに相当します。

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