Ontario Cancer Institute; University Health Network and Department of Medical Biophysics; University of Toronto; Toronto, Ontario, Canada.
Cell Cycle. 2013 Sep 1;12(17):2733-7. doi: 10.4161/cc.25785. Epub 2013 Aug 5.
Ubiquitylation is currently recognized as a major posttranslational modification that regulates diverse cellular processes. Pirh2 is a ubiquitin E3 ligase that regulates the turnover and functionality of several proteins involved in cell proliferation and differentiation, cell cycle checkpoints, and cell death. Here we review the role of Pirh2 as a regulator of the DNA damage response through the ubiquitylation of p53, Chk2, p73, and PolH. By ubiquitylating these proteins, Pirh2 regulates cell cycle checkpoints and cell death in response to DNA double-strand breaks or the formation of bulky DNA lesions. We also discuss how Pirh2 affects cell proliferation and differentiation in unstressed conditions through ubiquitylation and degradation of c-Myc, p63, and p27(kip1). Finally, we link these different functions of Pirh2 to its role as a tumor suppressor in mice and as a prognosis marker in various human cancer subtypes.
泛素化目前被认为是一种主要的翻译后修饰，可调节多种细胞过程。Pirh2 是一种泛素 E3 连接酶，可调节细胞增殖和分化、细胞周期检查点以及细胞死亡涉及的几种蛋白质的周转和功能。在这里，我们通过泛素化 p53、Chk2、p73 和 PolH 来综述 Pirh2 作为 DNA 损伤反应调节剂的作用。通过泛素化这些蛋白质，Pirh2 可调节细胞周期检查点和细胞死亡，以响应 DNA 双链断裂或大体积 DNA 损伤的形成。我们还讨论了 Pirh2 如何通过泛素化和降解 c-Myc、p63 和 p27(kip1)在未受应激的情况下影响细胞增殖和分化。最后，我们将 Pirh2 的这些不同功能与其在小鼠中的肿瘤抑制因子作用以及在各种人类癌症亚型中的预后标志物作用联系起来。
