Genovese C, Trani D, Caputi M, Claudio P P
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Oncogene. 2006 Aug 28;25(38):5201-9. doi: 10.1038/sj.onc.1209652.
Rb family proteins (pRb/p105, Rb2/p130 and p107) play a key role in cell cycle control and are worthily involved in transcription repression and tumor suppression. The mechanisms of transcriptional activation and repression by the Rb gene family has been extensively investigated: pRb, pRb2/p130 and p107 interact with different E2F family factors and can inhibit E2F responsive promoters, interfering with progression of cell cycle, gene transcription, initiation of apoptotic process and cell differentiation. Recent studies have indicated that Rb and Rb2/p130 may be involved in cellular response to DNA damage events, by influencing the transcription of factors involved in DNA repair pathways. In particular, evidences suggest that Rb loss and target gene deregulation impacts on the repair of UV-induced pyrimidine pyrimidone photoproducts (6-4 PP) by regulating the expression of several DNA damage factors involved in UV DNA damage repair processes, including proliferating cell nuclear antigen. Ongoing studies are focused on the mechanisms by which Rb family genes drive cell cycle exit following DNA damage induction, and how Rb gene family's interaction with chromatin remodeling factors can influence DNA repair dynamics.
Rb家族蛋白（pRb/p105、Rb2/p130和p107）在细胞周期调控中起关键作用，并且在转录抑制和肿瘤抑制方面也发挥着重要作用。Rb基因家族的转录激活和抑制机制已得到广泛研究：pRb、pRb2/p130和p107与不同的E2F家族因子相互作用，并能抑制E2F反应性启动子，干扰细胞周期进程、基因转录、凋亡过程的启动以及细胞分化。最近的研究表明，Rb和Rb2/p130可能通过影响参与DNA修复途径的因子的转录，从而参与细胞对DNA损伤事件的反应。特别是，有证据表明，Rb缺失和靶基因失调通过调节参与紫外线DNA损伤修复过程的几种DNA损伤因子（包括增殖细胞核抗原）的表达，影响紫外线诱导的嘧啶嘧啶酮光产物（6-4PP）的修复。正在进行的研究集中在Rb家族基因在DNA损伤诱导后驱动细胞周期退出的机制，以及Rb基因家族与染色质重塑因子的相互作用如何影响DNA修复动力学。
