Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
J Clin Invest. 2011 Apr;121(4):1263-5. doi: 10.1172/JCI57080. Epub 2011 Mar 14.
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.
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。
