hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas
hSSB1 binds and protects p21 from ubiquitin-mediated degradation and positively correlates with p21 in human hepatocellular carcinomas
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hSSB1 结合并保护 p21 免受泛素介导的降解，并与人肝细胞癌中的 p21 呈正相关
DOI：
10.1038/onc.2010.596
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发表时间：
2011-05-01
期刊：
影响因子：
8
通讯作者：
Kang, T.
中科院分区：
文献类型：
--
作者：
Xu, S.;Feng, Z.;Kang, T.
HSSB1是一种单链DNA结合蛋白，它的下调会导致辐射敏感性增加、检查点激活缺陷和基因组不稳定。然而，hSSB1在这些反应中的作用机制尚不清楚。在这里，我们提出了hSSB1直接与p21结合的证据，这种相互作用可能阻止p21由泛素介导的降解。此外，hSSB1基因敲除引起的G1/S转变的促进和G2/M检查点的消除都部分依赖于p21。最重要的是，通过免疫组织化学染色，hSSB1和p21在人肝细胞癌中的水平呈正相关。因此，hSSB1可能正向调控p21，调节细胞周期进程和DNA损伤反应，hSSB1有望成为治疗肝癌等癌症的新靶点。
Downregulation of hSSB1, a single-stranded DNA-binding protein, causes increased radiosensitivity, defective checkpoint activation and genomic instability. However, the mechanisms of hSSB1 function in these responses remain to be uncovered. Here, we present evidence that hSSB1 directly binds p21 and this interaction may prevent p21 from ubiquitin-mediated degradation. Furthermore, both promotion of the G1/S transition and abrogation of the G2/M checkpoints induced by hSSB1 knockdown are partially dependent on p21. Most importantly, hSSB1 and p21 levels are positively correlated in human hepatocellular carcinomas (HCC), as determined by immunostaining. Therefore, hSSB1 may positively modulate p21 to regulate cell cycle progression and DNA damage response, implicating hSSB1 as a novel, promising therapeutic target for cancers such as HCC.