Down-regulation of p21WAF1 promotes apoptosis in senescent human fibroblasts: involvement of retinoblastoma protein phosphorylation and delay of cellular aging

Journal of Cellular Physiology
Ying HuangTan Jun Tong

Abstract

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.

References

Jan 1, 1991·Mutation Research·J LindseyH J Cooke
May 31, 1990·Nature·C B HarleyC W Greider
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P DimriO Pereira-Smith
Apr 1, 1994·Journal of Cellular Biochemistry·E WangS Pandey
Dec 16, 1993·Nature·Y XiongD Beach
Jan 1, 1994·The Journal of Cell Biology·J C Reed
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·D L Vaux, A Strasser
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·D A AlcortaJ C Barrett
Aug 15, 1997·The Biochemical Journal·G M Cohen
Sep 15, 2001·Mechanisms of Ageing and Development·M SasakiY Mitsui
Sep 18, 2001·Journal of the American Geriatrics Society·A M Joaquin, S Gollapudi
Oct 19, 2001·The Journal of Biological Chemistry·J DuanT Tong

❮ Previous
Next ❯

Citations

Jun 29, 2006·Annals of the New York Academy of Sciences·Susumu Ohshima
Oct 8, 2005·Seminars in Oncology·Marcella MacalusoAntonio Giordano
May 24, 2016·Ageing Research Reviews·Mantas MatjusaitisAlexandra Stolzing
Mar 4, 2006·Journal of Cellular Biochemistry·Quan Hui ZhengTan Jun Tong
Apr 2, 2009·Expert Opinion on Therapeutic Targets·Sung Jin Ryu, Sang Chul Park
Jun 2, 2020·Frontiers in Cell and Developmental Biology·Jing LiuXiaoting Liang
Jan 22, 2019·International Journal of Biological Macromolecules·Qihong ZhangWeike Su

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis