| Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence. | |
| | |
MedLine Citation:
|
PMID: 16604064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Protein tyrosine phosphatases regulate important processes in eukaryotic cells and have critical functions in many human diseases including diabetes to cancer. 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. |
| | |
Authors:
|
Souad Rahmouni; Fabio Cerignoli; Andres Alonso; Toshiya Tsutji; Rachel Henkens; Changjun Zhu; Christine Louis-dit-Sully; Michel Moutschen; Wei Jiang; Tomas Mustelin |
Related Documents
:
|
18600804 - Long-term perfusion culture of hybridoma: a "grow or die" cell cycle system. 10475264 - Exposure to hyperbaric oxygen induces cell cycle perturbation in prostate cancer cells. 18783174 - Reverse engineering models of cell cycle regulation. 18540664 - Oviductal cell proteome alterations during the reproductive cycle in pigs. 8794924 - Monitoring exocytosis and release from individual mast cells by capillary electrophores... 11540624 - Orientation of the photosynthetic flagellate, peridinium gatunense, in hypergravity. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-04-09 |
Journal Detail:
|
Title: Nature cell biology Volume: 8 ISSN: 1465-7392 ISO Abbreviation: Nat. Cell Biol. Publication Date: 2006 May |
Date Detail:
|
Created Date: 2006-05-12 Completed Date: 2006-06-09 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 100890575 Medline TA: Nat Cell Biol Country: England |
Other Details:
|
Languages: eng Pagination: 524-31 Citation Subset: IM |
Affiliation:
|
The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals COS Cells Cell Aging / physiology* Cell Division / physiology* Cells, Cultured Cercopithecus aethiops DNA / biosynthesis Dual Specificity Phosphatase 3 Extracellular Signal-Regulated MAP Kinases / metabolism Hela Cells Humans JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Kinase Kinases / metabolism Protein Tyrosine Phosphatases / deficiency*, genetics, metabolism* RNA, Small Interfering / genetics S Phase / physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
AI35603/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/RNA, Small Interfering; 9007-49-2/DNA; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.25/MAP Kinase Kinase 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 |
| Comments/Corrections | |
Erratum In:
|
Nat Cell Biol. 2006 Jun;8(6):642 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension move...
Next Document: Individual dimers of the mitotic kinesin motor Eg5 step processively and support substantial loads i...