Department of Biochemistry & Molecular Biology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Metallomics. 2010 Jul;2(7):442-9. doi: 10.1039/c003915b. Epub 2010 May 18.
The p53 tumor suppressor is a transcription factor that contains a single zinc ion near its DNA binding interface. Zn(2+) is required for site-specific DNA binding and proper transcriptional activation. In addition to its functional significance, zinc plays a dominant role in determining whether p53 folds productively or misfolds. Insufficient zinc and excess zinc cause p53 to misfold by distinct mechanisms which both result in functional loss. The zinc-binding status of p53 in the cell is impacted significantly by the presence of tumorigenic mutations and by metal ion homeostasis. This review discusses mechanisms by which zinc modulates folding and misfolding of p53, how improper metal binding and release leads to loss of function and cancer, and how misfolding can be rescued by metallochaperones.
抑癌基因 p53 是一种转录因子，其 DNA 结合界面附近含有一个锌离子。Zn(2+) 对于特定的 DNA 结合和适当的转录激活是必需的。除了其功能意义之外，锌在决定 p53 是否折叠正确或错误方面起着主导作用。锌不足和锌过量通过不同的机制导致 p53 错误折叠，这两种机制都会导致功能丧失。肿瘤发生突变和金属离子稳态对细胞中 p53 的锌结合状态有显著影响。这篇综述讨论了锌如何调节 p53 的折叠和错误折叠，以及不当的金属结合和释放如何导致功能丧失和癌症，以及金属伴侣蛋白如何拯救错误折叠。
