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Down‐regulation of p21 WAF1 promotes apoptosis in senescent human fibroblasts: Involvement of retinoblastoma protein phosphorylation and delay of cellular aging
Author(s) -
Huang Ying,
Corbley Michael J.,
Tang Zuoqin,
Yang Long,
Peng Yong,
Zhang Zong Yu,
Tong Tan Jun
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20125
Subject(s) - apoptosis , phosphorylation , transfection , microbiology and biotechnology , cell cycle , senescence , retinoblastoma protein , biology , programmed cell death , cell , retinoblastoma , gene , cancer research , genetics
It has been suggested that genes which exercise checkpoint control during cell cycle traverse are equally important to the process of apoptotic cell death. In this study, we show that the key cell cycle regulatory gene p21 WAF1 is also involved in the execution of apoptosis. p21 WAF1 expression was down‐regulated during NaBu‐induced apoptosis of senescent normal diploid human 2BS fibroblasts. Conversely, when p21 WAF1 expression was actively suppressed in 2BS cells by a stably transfected antisense p21 WAF1 construct, apoptosis was accelerated and senescence was delayed, as shown by several markers of cell aging. Down‐regulation of p21 WAF1 by antisense caused an increase in the phosphorylation and inactivation of pRb. Phosphorylation of pRb was further enhanced upon induction of apoptosis by NaBu. Our results suggest that p21 WAF1 , acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli. © 2004 Wiley‐Liss, Inc.