Gao Xuejuan, Dan Songsong, Xie Yingying, Qin Huanhuan, Tang Donge, Liu Xiaohui, He Qing-Yu, Liu Langxia
Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, 510632, China.
J Cell Biochem. 2015 Jan;116(1):158-69. doi: 10.1002/jcb.24955.
Proliferating cell nuclear antigen (PCNA) is a processivity factor of DNA replication which plays critical roles in the regulation of DNA replication and repair. In this study, we show that PCNA interacts directly in vitro and in cells with 14-3-3ζ, an adaptor protein that regulates cell growth and response to DNA damage in eukaryotes. The interaction is mediated by at least two PCNA-binding sites on 14-3-3ζ, one of which is a novel non-canonical PIP (PCNA interacting protein) box. We find that DNA damages induced by UVC irradiation and MMS (methyl methanesulfonate) can enhance both the interaction of these two proteins and their co-localization with chromatin. Functional analyses suggest that 14-3-3ζ stabilizes PCNA possibly by regulating its ubiquitination, which impacts on DNA damage repair and cell viability.
增殖细胞核抗原（PCNA）是DNA复制的持续合成因子，在DNA复制和修复的调控中起关键作用。在本研究中，我们表明PCNA在体外和细胞内直接与14-3-3ζ相互作用，14-3-3ζ是一种衔接蛋白，在真核生物中调节细胞生长和对DNA损伤的反应。这种相互作用由14-3-3ζ上至少两个PCNA结合位点介导，其中一个是新型非典型PIP（PCNA相互作用蛋白）框。我们发现，紫外线照射和甲磺酸甲酯（MMS）诱导的DNA损伤可增强这两种蛋白的相互作用及其与染色质的共定位。功能分析表明，14-3-3ζ可能通过调节PCNA的泛素化来使其稳定，这会影响DNA损伤修复和细胞活力。
