Document Detail


Regulation of MAP kinases by the VHR dual-specific phosphatase: implications for cell growth and differentiation.
MedLine Citation:
PMID:  17012840     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although it is well established that a transient activation of the mitogen-activated protein kinases Erk and Jnk is a crucial step in most growth promoting signaling pathways, it has also been demonstrated that a prolonged activation of these kinases can induce differentiation, cell cycle arrest, and cell senescence. We recently found that the expression of the 21-kDa human Vaccinia H1-related (VHR) dual-specific phosphatase fluctuates during cell cycle progression and affects Erk and Jnk activity in a cell cycle-dependent manner. Cells lacking VHR arrested at the G(1)/S and G(2)/M transitions of the cell cycle and exhibited senescence phenotypes. Cells lacking VHR upregulated p21(Cip/Waf1) and downregulated many genes for cell cycle regulators, DNA replication, transcription, and mRNA processing. In the absence of VHR, the serum-induced activation of Jnk and Erk was further elevated and was required for the G(1)/S and G(2)/M blocks, which were attenuated upon Jnk and Erk inhibition. Collectively, VHR provides a long sought layer in the regulation of Jnk and Erk during cell cycle progression thereby contributing to cell cycle arrest, differentiation or senescence.
Authors:
Fabio Cerignoli; Souad Rahmouni; Ze'ev Ronai; Tomas Mustelin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2006-10-01
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  5     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-01-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2210-5     Citation Subset:  IM    
Affiliation:
The Burnham Institute for Medical Research, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle
Cell Cycle Proteins
Cell Differentiation
Cell Proliferation
Dual Specificity Phosphatase 3
Feedback, Physiological / physiology*
Humans
Mitogen-Activated Protein Kinases / metabolism*,  physiology
Protein Tyrosine Phosphatases / physiology*
Grant Support
ID/Acronym/Agency:
AI35603/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.1.3.48/DUSP3 protein, human; EC 3.1.3.48/Dual Specificity Phosphatase 3; EC 3.1.3.48/Protein Tyrosine Phosphatases

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


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