Department of Clinical Pharmacology, Medical Sciences Division, University of Oxford, Oxford, UK.
Oncogene. 2010 Apr 22;29(16):2357-67. doi: 10.1038/onc.2009.511. Epub 2010 Feb 8.
The pRb tumour suppressor protein has a central role in coordinating early cell cycle progression. An important level of control imposed on pRb occurs through post-translational modification, for example, phosphorylation. We describe here a new level of regulation on pRb, mediated through the targeted methylation of lysine residues, by the methyltransferase Set7/9. Set7/9 methylates the C-terminal region of pRb, both in vitro and in cells, and methylated pRb interacts with heterochromatin protein HP1. pRb methylation is required for pRb-dependent cell cycle arrest and transcriptional repression, as well as pRb-dependent differentiation. Our results indicate that methylation can influence the properties of pRb, and raise the interesting possibility that methylation modulates pRb tumour suppressor activity.
pRb 肿瘤抑制蛋白在协调早期细胞周期进展中具有核心作用。pRb 受到的重要控制水平是通过翻译后修饰（例如磷酸化）实现的。我们在这里描述了一种新的调节 pRb 的方式，即通过甲基转移酶 Set7/9 靶向赖氨酸残基的甲基化来实现。Set7/9 体外和细胞内均可甲基化 pRb 的 C 末端区域，并且甲基化的 pRb 与异染色质蛋白 HP1 相互作用。pRb 甲基化对于 pRb 依赖性细胞周期阻滞和转录抑制以及 pRb 依赖性分化是必需的。我们的结果表明，甲基化可以影响 pRb 的特性，并提出了一个有趣的可能性，即甲基化可以调节 pRb 肿瘤抑制活性。
