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Title: IL-1-induced ERK1/2 activation up-regulates p21{sup Waf1/Cip1} protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375

Abstract

IL-1 inhibits the proliferation of human melanoma cells A375 by arresting the cell cycle at G0/G1 phase, which accompanies the increase of p21{sup Waf1/Cip1} (p21) protein. Here, we demonstrate that IL-1 induces the stabilization of p21 protein via ERK1/2 pathway. The degradation of p21 was inhibited by IL-1, however the ubiquitination level of p21 was not affected. In addition, the degradation of non-ubiquitinated form of lysine less mutant p21-K6R was also inhibited by IL-1, suggesting that IL-1 stabilized p21 protein via ubiquitin-independent pathway. Furthermore, the inhibition of p21 protein degradation was prevented by a selective inhibitor of ERK1/2 pathway, PD98059. These results suggest that IL-1-induced ERK1/2 activation leads to the up-regulation of p21 by inhibiting degradation via ubiquitin-independent pathway in human melanoma cells A375.

Authors:
 [1];  [2]; ;  [1];  [1]
  1. Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan)
  2. Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan)
Publication Date:
OSTI Identifier:
22202371
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 392; Journal Issue: 3; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; CELL PROLIFERATION; INHIBITION; LYSINE; MELANOMAS; MUTANTS; PROTEINS

Citation Formats

Arakawa, Tomohiro, Hayashi, Hidetoshi, Itoh, Saotomo, Takii, Takemasa, and Onozaki, Kikuo, E-mail: konozaki@phar.nagoya-cu.ac.jp. IL-1-induced ERK1/2 activation up-regulates p21{sup Waf1/Cip1} protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.01.027.
Arakawa, Tomohiro, Hayashi, Hidetoshi, Itoh, Saotomo, Takii, Takemasa, & Onozaki, Kikuo, E-mail: konozaki@phar.nagoya-cu.ac.jp. IL-1-induced ERK1/2 activation up-regulates p21{sup Waf1/Cip1} protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375. United States. doi:10.1016/J.BBRC.2010.01.027.
Arakawa, Tomohiro, Hayashi, Hidetoshi, Itoh, Saotomo, Takii, Takemasa, and Onozaki, Kikuo, E-mail: konozaki@phar.nagoya-cu.ac.jp. Fri . "IL-1-induced ERK1/2 activation up-regulates p21{sup Waf1/Cip1} protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375". United States. doi:10.1016/J.BBRC.2010.01.027.
@article{osti_22202371,
title = {IL-1-induced ERK1/2 activation up-regulates p21{sup Waf1/Cip1} protein by inhibition of degradation via ubiquitin-independent pathway in human melanoma cells A375},
author = {Arakawa, Tomohiro and Hayashi, Hidetoshi and Itoh, Saotomo and Takii, Takemasa and Onozaki, Kikuo, E-mail: konozaki@phar.nagoya-cu.ac.jp},
abstractNote = {IL-1 inhibits the proliferation of human melanoma cells A375 by arresting the cell cycle at G0/G1 phase, which accompanies the increase of p21{sup Waf1/Cip1} (p21) protein. Here, we demonstrate that IL-1 induces the stabilization of p21 protein via ERK1/2 pathway. The degradation of p21 was inhibited by IL-1, however the ubiquitination level of p21 was not affected. In addition, the degradation of non-ubiquitinated form of lysine less mutant p21-K6R was also inhibited by IL-1, suggesting that IL-1 stabilized p21 protein via ubiquitin-independent pathway. Furthermore, the inhibition of p21 protein degradation was prevented by a selective inhibitor of ERK1/2 pathway, PD98059. These results suggest that IL-1-induced ERK1/2 activation leads to the up-regulation of p21 by inhibiting degradation via ubiquitin-independent pathway in human melanoma cells A375.},
doi = {10.1016/J.BBRC.2010.01.027},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 392,
place = {United States},
year = {Fri Feb 12 00:00:00 EST 2010},
month = {Fri Feb 12 00:00:00 EST 2010}
}