Linked Life Data

17785458

Source:http://linkedlifedata.com/resource/pubmed/id/17785458

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2007-10-22
pubmed:abstractText
Phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) is mediated by a family of kinases that respond to various forms of environmental stress. The eIF2alpha kinases are critical for mRNA translation, cell proliferation, and apoptosis. Activation of the tumor suppressor p53 results in cell cycle arrest and apoptosis in response to various types of stress. We previously showed that, unlike the majority of stress responses that stabilize and activate p53, induction of endoplasmic reticulum stress leads to p53 degradation through an Mdm2-dependent mechanism. Here, we demonstrate that the endoplasmic reticulum-resident eIF2alpha kinase PERK mediates the proteasomal degradation of p53 independently of translational control. This role is not specific for PERK, because the eIF2alpha kinase PKR also promotes p53 degradation in response to double-stranded RNA. We further establish that the eIF2alpha kinases induce glycogen synthase kinase 3 to promote the nuclear export and proteasomal degradation of p53. Our findings reveal a novel cross-talk between the eIF2alpha kinases and p53 with implications in cell proliferation and tumorigenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31675-87
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The eIF2alpha kinases PERK and PKR activate glycogen synthase kinase 3 to promote the proteasomal degradation of p53.
pubmed:affiliation
Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't