Joubel Anita, Chalkley Robert J, Medzihradszky Katalin F, Hondermarck Hubert, Burlingame Alma L
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158-2517, USA.
Mol Cell Proteomics. 2009 Jun;8(6):1167-73. doi: 10.1074/mcp.M800487-MCP200. Epub 2009 Jan 19.
The p53 tumor suppressor protein is a key regulator of cell cycle and death that is involved in many cell signaling pathways and is tightly regulated in mammalian cells. Post-translational modifications of p53 have been investigated previously mainly using antibodies. In this study, utilizing LC-MS/MS analysis, we have characterized p53 protein from COS-1 cells. Several already known post-translational modifications were observed, such as phosphorylation on serines 15, 33, 315, and 392 as well as acetylation on lysines 305, 370, 372, 373, 381, 382, and 386. Interestingly novel acetylation sites were identified at lysines 319 and 357. This study confirmed that p53 is a highly acetylated protein and revealed new acetylation sites that might aid the further understanding of p53 regulation.
p53肿瘤抑制蛋白是细胞周期和细胞死亡的关键调节因子,参与多种细胞信号通路,在哺乳动物细胞中受到严格调控。此前对p53的翻译后修饰研究主要使用抗体。在本研究中,我们利用液相色谱-串联质谱(LC-MS/MS)分析对COS-1细胞中的p53蛋白进行了表征。观察到了几种已知的翻译后修饰,如丝氨酸15、33、315和392位点的磷酸化以及赖氨酸305、370、372、373、381、382和386位点的乙酰化。有趣的是,在赖氨酸319和357位点发现了新的乙酰化位点。本研究证实p53是一种高度乙酰化的蛋白,并揭示了可能有助于进一步理解p53调控的新乙酰化位点。