UHRF2通过其环状结构域降低p21水平来促进DNA损伤反应。

UHRF2 promotes DNA damage response by decreasing p21 via RING finger domain.

作者信息

Wang Yangyang, Yan Xinke, Zeng Shengyuan, Zhang Ting, Cheng Fengjuan, Chen Rongjuan, Duan Changzhu

机构信息

Department of Cell Biology and Genetics, Molecular Medicine and Cancer Research Center, Chongqing Medical University, No. 1, Medical School Road, Chongqing, 400016, China.

Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics Center, Linkoping University, 58183, Linkoping, Sweden.

出版信息

Biotechnol Lett. 2018 Aug;40(8):1181-1188. doi: 10.1007/s10529-018-2577-5. Epub 2018 Jun 19.

DOI:10.1007/s10529-018-2577-5

PMID:29923055

Abstract

OBJECTIVES

To investigate the interaction of E3 ubiquitin ligase UHRF2 with p21 and the mechanism of UHRF2 in repairing DNA damage caused by hydroxyurea (HU) in HEK293 cells.

RESULTS

Western blotting indicated that the overexpression of UHRF2 reduced the level of p21, particularly in HEK293 cells. Immunoprecipitation and immunofluorescence staining reveled that UHRF2 combined with p21 in the nucleus. In addition, UHRF2 degraded p21 through ubiquitination and shortened the half-life of p21. UHRF2 could repair DNA damage caused by HU treatment, which was impaired by the inhibition of p21 in HEK293 cells.

CONCLUSIONS

UHRF2 may negatively modulate p21 to regulate DNA damage response, suggesting a novel pathway of UHRF2 repairing DNA damage through the partial regulation of p21.

摘要

目的

研究E3泛素连接酶UHRF2与p21的相互作用以及UHRF2在人胚肾293（HEK293）细胞中修复羟基脲（HU）所致DNA损伤的机制。

结果

蛋白质免疫印迹法表明，UHRF2的过表达降低了p21的水平，在HEK293细胞中尤为明显。免疫沉淀和免疫荧光染色显示，UHRF2与p21在细胞核中结合。此外，UHRF2通过泛素化降解p21并缩短了p21的半衰期。UHRF2能够修复HU处理所致的DNA损伤，而在HEK293细胞中抑制p21会损害这种修复作用。