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Regulation of p21 waf1/cip1 Expression by Intracellular Redox Conditions
Author(s) -
Esposito Franca,
Russo Lucia,
Chirico Giuseppa,
Ammendola Rosario,
Russo Tommaso,
Cimino Filiberto
Publication year - 2001
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540252774793
Subject(s) - intracellular , reactive oxygen species , microbiology and biotechnology , redox , dephosphorylation , chemistry , signal transduction , mapk/erk pathway , cell growth , oxidative phosphorylation , oxidative stress , homeostasis , biochemistry , biophysics , phosphorylation , biology , phosphatase , organic chemistry
Reactive oxygen species (ROS) have been considered for a long time only as molecules for inducing oxidative damage to proteins, lipids, and nucleic acids. However, in the last few years some physiological effects of ROS have been hypothesized, consisting of the redox regulation of several biological processes, including the transduction of mitogenic signals. This means that intracellular generation of ROS could be necessary to maintain homeostasis, as well as that their formation/scavenging should be controlled processes. We developed an experimental procedure that causes redox perturbations in intact cells, based on the exposure of living cells to diethylmaleate (DEM), a GSH‐depleting agent. By this procedure we demonstrated that ROS generated following DEM treatment induces a G1 arrest, that is accompanied by several redoxdependent changes in cell cycle‐related proteins. One of these is the p53‐independent accumulation of p21 waf1/cip1, which requires the integrity of the ras ‐MAPK pathway. Accordingly, DEM treatment strongly activates ERK2. On the other hand, redox perturbations provoked by DEM induce several early phenomena, including p21 waf1/cip1 and Rb dephosphorylation.