HJURP Regulates Cellular Senescence in Human Fibroblasts and Endothelial Cells Via a p53-Dependent Pathway

被引：20
作者：
Heo, Jong-Ik [1 ]
Cho, Jung Hee [1 ]
Kim, Jae-Ryong [1 ]
机构：
[1] Yeungnam Univ, Coll Med, Aging Associated Vasc Dis Res Ctr, Dept Biochem & Mol Biol, Taegu 705717, South Korea
来源：
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2013年 / 68卷 / 08期
基金：
新加坡国家研究基金会;
关键词：
Holliday junction recognition protein; Cellular senescence; p53; Human primary cells; CENP-A; IONIZING-RADIATION; CANCER;
D O I：
10.1093/gerona/gls257
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
Holliday junction recognition protein (HJURP), a centromere protein-A (CENP-A) histone chaperone, mediates centromere-specific assembly of CENP-A nucleosome, contributing to high-fidelity chromosome segregation during cell division. However, the role of HJURP in cellular senescence of human primary cells remains unclear. We found that the expression levels of HJURP decreased in human dermal fibroblasts and umbilical vein endothelial cells in replicative or premature senescence. Ectopic expression of HJURP in senescent cells partially overcame cell senescence. Conversely, downregulation of HJURP in young cells led to premature senescence. p53 knockdown, but not p16 knockdown, abolished senescence phenotypes caused by HJURP reduction. These data suggest that HJURP plays an important role in the regulation of cellular senescence through a p53-dependent pathway and might contribute to tissue or organismal aging and protection of cellular transformation.
引用
收藏
页码：914 / 925
页数：12
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