Reference : Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/4829
Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence
English
Rahmouni, Souad mailto [Université de Liège - ULg > Département des sciences cliniques > Immunopathologie - Transplantation >]
Cerignoli, Fabio [> > > >]
Alonso, Andres [> > > >]
Tsutji, Toshiya [> > > >]
Henkens, Rachel [Université de Liège - ULg > > Immunopathologie - Transplantation >]
Zhu, Changjun [> > > >]
Louis-dit-Sully, Christine [> > > >]
Moutschen, Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Immunopathologie - Transplantation]
Jiang, Wei [> > > >]
Mustelin, Tomas [> > > >]
May-2006
Nature Cell Biology
Nature Publishing Group
8
5
524-U178
Yes (verified by ORBi)
International
1465-7392
London
[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.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/4829

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