Linked Life Data

17452332

Source:http://linkedlifedata.com/resource/pubmed/id/17452332

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2007-6-18
pubmed:abstractText
In response to DNA damage, p53 and its homolog p73 have a function antagonistic to NF-kappaB in deciding cell fate. Here, we show for the first time that p73, but not p53, is stabilized by physical interaction with nuclear IkappaB kinase (IKK)-alpha to enhance cisplatin (CDDP)-induced apoptosis. CDDP caused a significant increase in the amounts of nuclear IKK-alpha and p73alpha in human osteosarcoma-derived U2OS cells. Ectopic expression of IKK-alpha prolonged the half-life of p73 by inhibiting its ubiquitination and thereby enhancing its transactivation and pro-apoptotic activities. Consistent with these results, small interfering RNA-mediated knockdown of endogenous IKK-alpha inhibited the CDDP-mediated accumulation of p73alpha. The kinase-deficient mutant form of IKK-alpha interacted with p73alpha, but failed to stabilize it. Furthermore, CDDP-mediated accumulation of endogenous p73alpha was not detected in mouse embryonic fibroblasts (MEFs) prepared from IKK-alpha-deficient mice, and CDDP sensitivity was significantly decreased in IKK-alpha-deficient MEFs compared with wild-type MEFs. Thus, our results strongly suggest that the nuclear IKK-alpha-mediated accumulation of p73alpha is one of the novel molecular mechanisms to induce apoptotic cell death in response to CDDP, which may be particularly important in killing tumor cells with p53 mutation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18365-78
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Stabilization of p73 by nuclear IkappaB kinase-alpha mediates cisplatin-induced apoptosis.
pubmed:affiliation
Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't