好的 COP1 还是坏的 COP1？体内见真知。
Good COP1 or bad COP1? In vivo veritas.
机构信息
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
J Clin Invest. 2011 Apr;121(4):1263-5. doi: 10.1172/JCI57080. Epub 2011 Mar 14.
Abstract
The evolutionarily conserved protein COP1 has been shown to operate as an E3 ubiquitin ligase complex, and a number of putative substrates have been identified, including the c-JUN oncoprotein and p53 tumor suppressor protein. New work by Migliorini and colleagues described in the current issue of JCI demonstrates that COP1 acts as a tumor suppressor in vivo and does so, at least in part, by promoting the destruction of c-JUN. These findings challenge the view that COP1 regulates p53 stability and call into question the wisdom of developing COP1 inhibitors as potential anticancer agents.
摘要
进化上保守的 COP1 蛋白已被证明作为 E3 泛素连接酶复合物发挥作用，并且已经鉴定出许多假定的底物，包括 c-JUN 癌蛋白和 p53 肿瘤抑制蛋白。Migliorini 及其同事在本期 JCI 中描述的新工作表明，COP1 在体内作为肿瘤抑制剂发挥作用，至少部分是通过促进 c-JUN 的破坏来实现的。这些发现挑战了 COP1 调节 p53 稳定性的观点，并质疑了将 COP1 抑制剂作为潜在抗癌药物开发的明智性。
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本文引用的文献
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Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice.COP1 组成性调节 c-Jun 蛋白稳定性，并在小鼠中作为肿瘤抑制因子发挥作用。
J Clin Invest. 2011 Apr;121(4):1329-43. doi: 10.1172/JCI45784. Epub 2011 Mar 14.
2
Regulation of transcription factor function by targeted protein degradation: an overview focusing on p53, c-Myc, and c-Jun.通过靶向蛋白质降解对转录因子功能的调控：聚焦于p53、c-Myc和c-Jun的综述
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The E3 ubiquitin ligase complex component COP1 regulates PEA3 group member stability and transcriptional activity.E3 泛素连接酶复合物组件 COP1 调节 PEA3 家族成员的稳定性和转录活性。
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E3 ubiquitin ligase COP1 regulates the stability and functions of MTA1.E3泛素连接酶COP1调节MTA1的稳定性和功能。
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RING domain E3 ubiquitin ligases.环状结构域E3泛素连接酶
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COP1 functions as a FoxO1 ubiquitin E3 ligase to regulate FoxO1-mediated gene expression.COP1作为一种FoxO1泛素E3连接酶发挥作用，以调节FoxO1介导的基因表达。
J Biol Chem. 2008 Dec 19;283(51):35464-73. doi: 10.1074/jbc.M801011200. Epub 2008 Sep 24.
7
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Cancer Cell. 2007 Apr;11(4):361-74. doi: 10.1016/j.ccr.2007.02.007.
10
ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage.DNA损伤后，共济失调毛细血管扩张突变蛋白（ATM）促使E3泛素连接酶COP1发生自降解。
Science. 2006 Aug 25;313(5790):1122-6. doi: 10.1126/science.1127335.
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