Linked Life Data

18502749

Source:http://linkedlifedata.com/resource/pubmed/id/18502749

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
2008-7-16
pubmed:abstractText
Macrophage migration inhibitory factor (MIF) is a potent modulator of the p53 signaling pathway, but the molecular mechanisms of the effect of MIF on p53 function have so far remained unclear. Here we show that MIF physically interacts with the p53 tumor suppressor in vitro and in vivo. This association was significantly reduced by a C81S mutation but not C57S or C60S mutations, suggesting that Cys(81) is essential for the in vivo association between MIF and p53. This association also depended on Cys(242) (and, to some extent, on Cys(238)) within the central DNA binding domain of p53. Ectopic expression of MIF, but not MIF(C81S), inhibited p53-mediated transcriptional activation in a dose-dependent manner. Conversely, knockdown of endogenous MIF stimulated p53-mediated transcription. MIF inhibited p53-induced apoptosis and cell cycle arrest, whereas the MIF(C81S) mutant, which is unable to physically associate with p53, had no effect. Consistent with these findings, confocal microscopy showed that MIF prevented p53 translocation from the cytoplasm to the nucleus. We also demonstrated that MIF suppresses p53 activity by stabilizing the physical association between p53 and Mdm2. These results suggest that MIF physically associates with p53 and negatively regulates p53 function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20383-96
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Critical role of cysteine residue 81 of macrophage migration inhibitory factor (MIF) in MIF-induced inhibition of p53 activity.
pubmed:affiliation
Department of Biochemistry, Biotechnology Research Institute, School of Life Sciences, Chungbuk National University, Cheongju, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't