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Differential regulation of p21 by p53 and Rb in cellular response to oxidative stress
Author(s) -
Yin Yuxin,
Solomon Gregory,
Deng Chuxia,
Barrett J. Carl
Publication year - 1999
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199901)24:1<15::aid-mc3>3.0.co;2-y
Subject(s) - programmed cell death , oxidative stress , biology , microbiology and biotechnology , transactivation , ectopic expression , apoptosis , cell fate determination , retinoblastoma protein , cell , oxidative phosphorylation , cell growth , cell cycle , cell culture , transcription factor , genetics , gene , biochemistry
Oxidative stress to mammalian cells causes cellular damage and triggers inducible cellular responses leading to cell death by apoptosis. In this paper, we report that p53 was required for programmed cell death induced by oxidative stress in both mouse and human cells and that p53 transactivation was involved in induction of oxidative cell death. Furthermore, we show that p21 was highly responsive to oxidative stress in a p53‐dependent manner and that ectopic expression of p21 could increase cellular susceptibility to oxidative stress in the absence of p53. However, p21 was not required for p53‐directed oxidative cell death because mouse embryo fibroblasts MEFs lacking p21( p21 –/– MEFs) were still susceptible to oxidative cell death. Interestingly, bax, a cell‐death mediator regulated by p53, was overexpressed in p21 –/– MEFs that underwent cell death by oxidative stress, suggesting a compensation for loss of p21 that may be responsible for the existence of cell‐death responses in p21 ‐knockout mouse fibroblasts. Finally, we provide evidence that the retinoblastoma gene product (Rb) is a negative regulator of p21 and a repressor of the cellular apoptotic process. Because p21 is regulated by p53 positively and by Rb negatively, p21 may be a link between p53 and Rb in determining cell fate after oxidative damage. Mol. Carcinog. 24:15–24, 1999. © 1999 Wiley‐Liss, Inc.