[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Cerignoli, Fabio
Rahmouni, Souad ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Ronai, Ze'ev
Mustelin, Tomas
Language :
English
Title :
Regulation of MAP kinases by the VHR dual-specific phosphatase: implications for cell growth and differentiation.
Publication date :
2006
Journal title :
Cell Cycle
ISSN :
1538-4101
eISSN :
1551-4005
Publisher :
Landes Bioscience, Georgetown, United States - Texas
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