Linked Life Data

17965021

Source:http://linkedlifedata.com/resource/pubmed/id/17965021

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2007-12-24
pubmed:abstractText
Lysophosphatidic acid (LPA) promotes cell survival through the activation of G protein-coupled LPA receptors. However, whether different LPA receptors activate distinct anti-apoptotic signaling pathways is not yet clear. Here we report a novel mechanism by which the LPA(2) receptor targets the proapoptotic Siva-1 protein for LPA-dependent degradation, thereby attenuating Siva-1 function in DNA damage response. The carboxyl-terminal tail of the LPA(2) receptor, but not LPA(1) or LPA(3) receptor, specifically associates with the carboxyl cysteine-rich domain of Siva-1. Prolonged LPA stimulation promotes the association of Siva-1 with the LPA(2) receptor and targets both proteins for ubiquitination and degradation. As a result, adriamycin-induced Siva-1 protein stabilization is attenuated by LPA in an LPA(2)-dependent manner, and the function of Siva-1 in promoting DNA damage-induced apoptosis is inhibited by LPA pretreatment. Consistent with this result, inhibition of the LPA(2) receptor expression increases Siva-1 protein levels and augments adriamycin-induced caspase-3 cleavage and apoptosis. Together, these findings reveal a critical and specific role for the LPA(2) receptor through which LPA directly inactivates a critical component of the death machinery to promote cell survival.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37759-69
pubmed:dateRevised
2011-4-26
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The lysophosphatidic acid 2 receptor mediates down-regulation of Siva-1 to promote cell survival.
pubmed:affiliation
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. flin@uab.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural