USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 tosuppress cell apoptosis and is required for mouse embryonic development (Molecular Cell, 2012, 46:484-496)

報告日期: 2012/11/16
報告時間: 16:00/16:50
報告學生: 王毅昌
講評老師: 呂增宏
附件下載: 下載[1245-1348734484-1.pdf] 

 

USP22 Antagonizes p53 Transcriptional Activation by Deubiquitinating Sirt1 to Suppress Cell Apoptosis and Is Required for Mouse Embryonic Development

Zhenghong Lin,Heeyoung Yang,Qingfei Kong,Jinping Li,Sang-Myeong Lee,Beixue Gao,Hongxin Dong,

Jianjun WeiJianxun Song,Donna D. Zhang,and Deyu Fang.

Molecular Cell 2012; May.46, 484-494.

Speaker: Yi-Chang Wang                                        Date: 2012.11.16.

Commentator: Dr. Tzeng-Horng Leu                                 Place: Room 602

 

Abstarct:

Sirt1 is a NAD-dependent histone deacetylase which can deacetylate a variety of proteins including histones H1, H3, and H4. Many other proteins can also serve as substrates for Sirt1, including p53, FOXO, Ku70, p300, Rb, E2F1, NF-kB, and AP-1. Therefore, Sirt1 can regulate diverse cellular processes ranging from stress response, aging, and immunity to cancer. The authors identified several Sirt1-interacting proteins, including ubiquitin-specific peptidase 22 (USP22), from immunoprecipitation in HEK293 cells. Previous study has found that the USP22 can reverse ubiquitination of H2A, H2B, and TRF1 to regulate cell-cycle and apoptosis. For this reason, the authors wanted to clarity the possibility that USP22 promotes cell proliferation and suppresses apoptosis through regulation of Sirt1 to anatagonize p53 function. First, the authors found that USP22 binds Sirt1 via its N-terminal zinc finger domain to suppress Sirt1 ubiquitination, and prolonged the half-life of Sirt1.The authors also found that USP22 can inhibit the levels of acetylation but not protein expression of p53, and abate the transcriptional activity and pro-apoptotic function of p53 through deubiquitination of Sirt1. Finally, by generating usp22 knockout mice, the authors found that USP22 appears to be critical for early stages of embryonic development through its suppression of p53 transcriptional activity and suppression of cell apoptosis functions.

References:

1.    Sowa, M.E., Bennett, E.J., Gygi, S.P., and Harper, J.W. (2009). Defining the human deubiquitinating enzyme interaction landscape. Cell 138, 389–403.

2.    Zhang, X.Y., Varthi, M., Sykes, S.M., Phillips, C., Warzecha, C., Zhu, W., Wyce, A., Thorne, A.W., Berger, S.L., and McMahon, S.B. (2008). The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol. Cell 29, 102–111.