Linked Life Data

17210576

Source:http://linkedlifedata.com/resource/pubmed/id/17210576

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-3-5
pubmed:abstractText
ATM and Rad3-related (ATR) is a regulatory kinase that, when activated by hydroxyurea, UV, or human immunodeficiency virus-1 Vpr, causes cell cycle arrest through Chk1-Ser(345) phosphorylation. We demonstrate here that of these three agents only Vpr requires protein phosphatase type 2A (PP2A) to activate ATR for Chk1-Ser(345) phosphorylation. A requirement for PP2A by Vpr was first shown with the PP2A-specific inhibitor okadaic acid, which reduced Vpr-induced G(2) arrest and Cdk1-Tyr(15) phosphorylation. Using small interference RNA to down-regulate specific subunits of PP2A indicated that the catalytic beta-isoform PP2A(Cbeta) and the A regulatory alpha-isoform PP2A(Aalpha) are involved in the G(2) induction, and these downregulations decreased the Vpr-induced, ATR-dependent phosphorylations of Cdk1-Tyr(15) and Chk1-Ser(345). In contrast, the same down-regulations had no effect on hydroxyurea- or UV-activated ATR-dependent Chk1-Ser(345) phosphorylation. Vpr and hydroxyurea/UV all induce ATR-mediated gammaH2AX-Ser(139) phosphorylation and foci formation, but down-regulation of PP2A(Aalpha) or PP2A(Cbeta) did not decrease gammaH2AX-Ser(139) phosphorylation by any of these agents or foci formation by Vpr. Conversely, H2AX down-regulation had little effect on PP2A(Aalpha/Cbeta)-mediated G(2) arrest and Chk1-Ser(345) phosphorylation by Vpr. The expression of vpr increases the amount and phosphorylation of Claspin, an activator of Chk1 phosphorylation. Down-regulation of either PP2A(Cbeta) or PP2A(Aalpha) had little effect on Claspin phosphorylation, but the amount of Claspin was reduced. Claspin may then be one of the phosphoproteins through which PP2A(Aalpha/Cbeta) affects Chk1 phosphorylation when ATR is activated by human immunodeficiency virus-1 Vpr.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ATR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/CLSPN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Checkpoint kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, vpr, http://linkedlifedata.com/resource/pubmed/chemical/H2AFX protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Histones, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyurea, http://linkedlifedata.com/resource/pubmed/chemical/PPP2CA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7287-98
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Phosphatase type 2A-dependent and -independent pathways for ATR phosphorylation of Chk1.
pubmed:affiliation
Department of Pathology, Department of Microbiology-Immunology, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural