Linked Life Data

16786187

Source:http://linkedlifedata.com/resource/pubmed/id/16786187

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2006-11-30
pubmed:abstractText
Ultraviolet light (UV) inhibits translation initiation through activation of kinases that phosphorylate the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha). Two eIF2alpha kinases, PERK and GCN2, are known to phosphorylate the Serine-51 of eIF2alpha in response to UV-irradiation. In this report, we present evidence that phosphorylation of eIF2alpha plays a role in UV-induced apoptosis. Our data show that wild-type mouse embryo fibroblasts (MEF(s/s)) are less sensitive to UV-induced apoptosis than MEF(A/A) cells in which the phosphorylation site, Ser51, of eIF2alpha is replaced with a non-phosphorylatable Ala (Ser51Ala). PARP expression in MEF(A/A) cells is reduced without being cleaved after UV-irradiation. In contrast, PARP is cleaved without a significant decrease in parental PARP in MEF(S/S) cells after UV-irradiation. Our data also show that MEF(GCN2-/-) cells, in which GCN2 is knocked out, are more sensitive to UV-irradiation, agreeing with the observation from MEF(A/A) cells. However, MEF(PERK-/-) cells, in which PERK is knocked out, are less sensitive to UV-irradiation. In addition, MCF-7-PERKDeltaC cells, which are stably transfected with a kinase domain deleted mutant of PERK (PERKDeltaC), are more resistant to UV-induced apoptosis than parental MCF-7 cells. Overexpression of wild-type PERK sensitizes MCF-7 cells to UV-induced apoptosis without directly inducing cell death. These results suggest that the level of eIF2alpha phosphorylation impacts PARP expression upon UV-irradiation. The eIF2alpha kinases may mediate UV-induced apoptosis via an eIF2alpha dependent or independent signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0300-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-81
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The roles of translation initiation regulation in ultraviolet light-induced apoptosis.
pubmed:affiliation
Department of Chemistry and Biochemistry and Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural