Article (Scientific journals)
Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence
Rahmouni, Souad; Cerignoli, Fabio; Alonso, Andres et al.
2006In Nature Cell Biology, 8 (5), p. 524-U178
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Abstract :
[en] Protein tyrosine phosphatases regulate important processes in eukaryotic cells and have critical functions in many human diseases including diabetes to cancer(1-3). Here, we report that the human Vaccinia H1-related (VHR) dual-specific protein tyrosine phosphatase regulates cell-cycle progression and is itself modulated during the cell cycle. Using RNA interference (RNAi), we demonstrate that cells lacking VHR arrest at the G1-S and G2-M transitions of the cell cycle and show the initial signs of senescence, such as flattening, spreading, appearance of autophagosomes, beta-galactosidase staining and decreased telomerase activity. In agreement with this notion, cells lacking VHR were found to upregulate p21(Cip-Waf1), whereas they downregulated the expression of genes for cell-cycle regulators, DNA replication, transcription and mRNA processing. Loss of VHR also caused a several-fold increase in serum-induced activation of its substrates, the mitogen-activated protein ( MAP) kinases Jnk and Erk. VHR-induced cell-cycle arrest was dependent on this hyperactivation of Jnk and Erk, and was reversed by Jnk and Erk inhibition or knock-down. We conclude that VHR is required for cell-cycle progression as it modulates MAP kinase activation in a cell-cycle phase-dependent manner.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Cerignoli, Fabio
Alonso, Andres
Tsutji, Toshiya
Henkens, Rachel ;  Université de Liège - ULiège > Immunopathologie - Transplantation
Zhu, Changjun
Louis-dit-Sully, Christine
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation
Jiang, Wei
Mustelin, Tomas
Language :
English
Title :
Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence
Publication date :
May 2006
Journal title :
Nature Cell Biology
ISSN :
1465-7392
eISSN :
1476-4679
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
8
Issue :
5
Pages :
524-U178
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 January 2009

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