Source:http://linkedlifedata.com/resource/pubmed/id/21521943
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2011-5-24
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pubmed:abstractText |
The dual-specificity phosphatase hYVH1 (DUSP12) is an evolutionary conserved phosphatase that also contains a unique zinc-binding domain. Recent evidence suggests that this enzyme plays a role in cell survival and ribosome biogenesis. Here, we report that hYVH1 expression also affects cell cycle progression. Overexpression of hYVH1 caused a significant increase in polyploidy and in the G 2/M cell population, with a subsequent decrease in the G 0/G 1 population. Phosphatase activity is dispensable, while the zinc-binding domain is necessary and sufficient for hYVH1-mediated cell cycle changes. In agreement with this, siRNA-mediated silencing of hYVH1 expression resulted in a dramatic increase in the G 0/G 1 population and susceptibility to cellular senescence. Additionally, mass spectrometry-based methods identified novel hYVH1 phosphorylation sites, including a C-terminal modification at position Ser ( 335) in the zinc-binding domain. Interestingly, phosphorylation at Ser335 regulates subcellular targeting of hYVH1 and augments the hYVH1 G 2/M phenotype. Collectively we demonstrate that hYVH1 is a novel modulator of cell cycle progression; a function mainly mediated by its C-terminal zinc-binding domain.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Dual-Specificity Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc,
http://linkedlifedata.com/resource/pubmed/chemical/dual specificity phosphatase 12
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1551-4005
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1669-78
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pubmed:dateRevised |
2011-11-4
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pubmed:meshHeading |
pubmed-meshheading:21521943-Cell Aging,
pubmed-meshheading:21521943-Cell Division,
pubmed-meshheading:21521943-Cell Line,
pubmed-meshheading:21521943-DNA,
pubmed-meshheading:21521943-Dual-Specificity Phosphatases,
pubmed-meshheading:21521943-G2 Phase,
pubmed-meshheading:21521943-Humans,
pubmed-meshheading:21521943-Phosphorylation,
pubmed-meshheading:21521943-Polyploidy,
pubmed-meshheading:21521943-Protein Binding,
pubmed-meshheading:21521943-Protein Structure, Tertiary,
pubmed-meshheading:21521943-RNA, Small Interfering,
pubmed-meshheading:21521943-RNA Interference,
pubmed-meshheading:21521943-Zinc
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pubmed:year |
2011
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pubmed:articleTitle |
The dual-specificity phosphatase hYVH1 (DUSP12) is a novel modulator of cellular DNA content.
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pubmed:affiliation |
University of Windsor, Windsor, Ontario, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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