Linked Life Data

7958853

Source:http://linkedlifedata.com/resource/pubmed/id/7958853

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
1994-11-30
pubmed:abstractText
The mdm2 proto-oncogene product binds to the p53 tumor suppressor protein and inhibits its ability to trans-activate target genes. One such target gene is mdm2 itself, which is therefore considered a component of a p53 negative feedback loop. Two tandem p53-binding motifs residing within the first intron of the murine mdm2 gene confer upon it p53-mediated activation. We now report that in murine cells p53 activates an internal mdm2 promoter (P2) located near the 3' end of intron 1, resulting in mRNA whose transcription starts within exon 2. P2 is activated by p53 within artificial constructs, as well as within the context of the chromosomal mdm2 gene. Activation follows either the introduction of overexpressed wild-type p53 into cells or the induction of endogenous wild-type p53 by ionizing radiation. The upstream, constitutive (P1) mdm2 promoter is only mildly affected by p53, if at all. The p53-derived mdm2 transcripts lack exon 1 and a few nucleotides from exon 2. As the first in-frame AUG of mdm2 is located within exon 3, the two types of mdm2 transcripts should possess similar coding potentials. Nevertheless, in vitro conditions, where each of these transcripts yields a distinct translation profile, reflect the differential usage of translation initiation codons. Initiation of translation at internal AUG codons, which occurs also in vivo, gives rise to MDM2 polypeptides incapable of binding to p53. In vitro translation profiles of the various mdm2 transcripts could be manipulated by changing the amounts of input RNA. Thus, p53 can modulate both the amount and the nature of MDM2 polypeptides through activation of the internal P2 promoter.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0890-9369
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
8
pubmed:geneSymbol
p53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1739-49
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential.
pubmed:affiliation
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't