Τίτλος:
CHOP-dependent regulation of p21/waf1 during ER stress
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The transcription factor CHOP/GADD153 is induced during the unfolded protein response (UPR) and is associated to the induction of ER stress-related apoptosis. However, how the transition between the pro-survival and the pro-apoptotic role of ER stress is being orchestrated remains poorly understood. Here we show that tunicamycin, an antibiotic promoting ER stress, suppresses the expression of p21, a tumor suppressor that induces cell cycle arrest and inhibits apoptosis. This suppression of p21 levels was independent of p53 that is the major transcriptional regulator of p21, but could be reproduced by forced expression of CHOP. Consistently with these findings, siRNA-mediated inhibition of p21 levels restored the sensitivity of CHOP-deficient cells to tunicamycin. Our findings are consistent with a CHOP-dependent role for p21 in the shift from the pro-survival to the pro-apoptotic function of UPR. Copyright © 2010 S. Karger AG, Basel.
Συγγραφείς:
Mihailidou, C.
Papazian, I.
Papavassiliou, A.G.
Kiaris, H.
Περιοδικό:
Cellular Physiology and Biochemistry
Εκδότης:
Cell Physiol Biochem Press
Λέξεις-κλειδιά:
cyclin dependent kinase inhibitor 1; growth arrest and DNA damage inducible protein 153; protein p21; protein p53; small interfering RNA; tunicamycin; antiinfective agent; Cdkn1a protein, mouse; cyclin dependent kinase inhibitor 1A; growth arrest and DNA damage inducible protein 153; tunicamycin, animal cell; apoptosis; article; cell cycle arrest; cell survival; controlled study; embryo; endoplasmic reticulum stress; genetic regulation; inhibition kinetics; mouse; nonhuman; phase transition; priority journal; protein expression; protein folding; protein function; protein induction; animal; cell line; drug effects; endoplasmic reticulum; fibroblast; gene expression regulation; genetics; metabolism, Animals; Anti-Bacterial Agents; Cell Line; Cyclin-Dependent Kinase Inhibitor p21; Endoplasmic Reticulum; Fibroblasts; Gene Expression Regulation; Mice; Transcription Factor CHOP; Tunicamycin
