Document Detail


p27 suppresses arsenite-induced Hsp27/Hsp70 expression through inhibiting JNK2/c-Jun- and HSF-1-dependent pathways.
MedLine Citation:
PMID:  20566634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p27 is an atypical tumor suppressor that can regulate the activity of cyclin-dependent kinases and G(0)-to-S phase transitions. More recent studies reveal that p27 may also exhibit its tumor-suppressive function through regulating many other essential cellular events. However, the molecular mechanisms underlying these anticancer effects of p27 are largely unknown. In this study, we found that depletion of p27 expression by either gene knock-out or knockdown approaches resulted in up-regulation of both Hsp27 and Hsp70 expression at mRNA- and promoter-derived transcription as well as protein levels upon arsenite exposure, indicating that p27 provides a negative signal for regulating the expression of Hsp27 and Hsp70. Consistently, arsenite-induced activation of JNK2/c-Jun and HSF-1 pathways was also markedly elevated in p27 knock-out (p27(-/-)) and knockdown (p27 shRNA) cells. Moreover, interference with the expression or function of JNK2, c-Jun, and HSF-1, but not JNK1, led to dramatic inhibition of arsenite-induced Hsp27 and Hsp70 expression. Collectively, our results demonstrate that p27 suppresses Hsp27 and Hsp70 expression at the transcriptional level specifically through JNK2/c-Jun- and HSF-1-dependent pathways upon arsenite exposure, which provides additional important molecular mechanisms for the tumor-suppressive function of p27.
Authors:
Jinyi Liu; Dongyun Zhang; Xiaoyi Mi; Qing Xia; Yonghui Yu; Zhenghong Zuo; Wei Guo; Xuewei Zhao; Jia Cao; Qing Yang; Angela Zhu; Wancai Yang; Xianglin Shi; Jingxia Li; Chuanshu Huang
Related Documents :
8197114 - Adipocyte differentiation selectively represses the serum inducibility of c-jun and jun...
11466704 - Characterization of murine batf: a negative regulator of activator protein-1 activity i...
1958524 - Oestrogen directly stimulates growth factor signal transduction pathways in human breas...
15135894 - Neurodegenerative and physiological actions of c-jun n-terminal kinases in the mammalia...
15897474 - Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucoco...
14739144 - Rapid induction of gata transcription factors in developing mouse intestine following g...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-06-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-09-30     Revised Date:  2011-08-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26058-65     Citation Subset:  IM    
Affiliation:
Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Arsenites / pharmacology*
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27 / physiology*
DNA-Binding Proteins / metabolism*
Fibroblasts
HSP27 Heat-Shock Proteins / analysis,  genetics*
HSP70 Heat-Shock Proteins / analysis,  genetics*
JNK Mitogen-Activated Protein Kinases / metabolism*
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase 9 / metabolism*
RNA, Messenger / analysis
Signal Transduction / drug effects
Teratogens
Transcription Factors / metabolism*
Transcriptional Activation / drug effects
Tumor Suppressor Proteins
Grant Support
ID/Acronym/Agency:
CA112557/CA/NCI NIH HHS; CA119028-05S110/CA/NCI NIH HHS; ES010344/ES/NIEHS NIH HHS; ES012451/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Arsenites; 0/DNA-Binding Proteins; 0/HSP27 Heat-Shock Proteins; 0/HSP70 Heat-Shock Proteins; 0/Hsf1 protein, mouse; 0/RNA, Messenger; 0/Teratogens; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 15502-74-6/arsenite; EC 2.7.1.24/Mitogen-Activated Protein Kinase 9; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Somatic nucleus reprogramming is significantly improved by m-carboxycinnamic acid bishydroxamide, a ...
Next Document:  Escherichia coli cell surface perturbation and disruption induced by antimicrobial peptides BP100 an...