Belal Hazrat, Ying Ng Esther Feng, Meitinger Franz
Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.
Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan.
Curr Opin Cell Biol. 2024 Dec;91:102424. doi: 10.1016/j.ceb.2024.102424. Epub 2024 Sep 7.
In recent years, the role of 53BP1 as a cell cycle regulator has come into the spotlight. 53BP1 is best understood for its role in controlling DNA double-strand break repair. However, 53BP1 was initially discovered as an interaction partner of the tumor suppressor p53, which proved to be independent of DNA repair. The importance of this interaction is becoming increasingly clear. 53BP1 responds to mitotic stress, which prolongs mitosis, or to DNA damage and triggers the stabilization of p53 by the deubiquitinase USP28 to stop the proliferation of potentially damaged cells. The ability of 53BP1 to respond to mitotic stress or DNA damage is controlled by cell cycle-specific post-translational modifications and is therefore restricted to specific cell cycle phases. 53BP1-mediated p53 activation is likely involved in tumor suppression and is associated with genetic diseases such as primary microcephaly. This review emphasizes the importance of these mechanisms for the development and maintenance of healthy tissues.
近年来，53BP1作为细胞周期调节因子的作用备受关注。53BP1在控制DNA双链断裂修复方面的作用最为人所熟知。然而，53BP1最初是作为肿瘤抑制因子p53的相互作用伙伴被发现的，后来证明这种作用与DNA修复无关。这种相互作用的重要性日益明显。53BP1对有丝分裂应激作出反应，这会延长有丝分裂过程，或者对DNA损伤作出反应，并通过去泛素化酶USP28触发p53的稳定，从而阻止潜在受损细胞的增殖。53BP1对有丝分裂应激或DNA损伤作出反应的能力受细胞周期特异性翻译后修饰的控制，因此仅限于特定的细胞周期阶段。53BP1介导的p53激活可能参与肿瘤抑制，并与诸如原发性小头畸形等遗传疾病有关。本综述强调了这些机制对健康组织发育和维持的重要性。
