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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
41
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pubmed:dateCreated |
1999-11-22
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pubmed:abstractText |
Overexpression of oncoprotein MDM2 has been found in a significant number of human soft tissue tumors. In a subset of these tumors, overexpression is a result of enhanced translation of mdm2 mRNA. There are two transcripts from the mdm2 gene that differ only in their 5' leaders: a long form (L-mdm2) and a short form (S-mdm2) that arise from the use of different promoters. L-mdm2 mRNA contains two upstream open reading frames (uORFs) and this mRNA was loaded with ribosomes inefficiently in comparison with S-mdm2. The 5' leader of L-mdm2 was sufficient to transfer translational repression to a reporter gene and the two uORFs acted synergistically to achieve full suppression. In contrast, the 5' leader of S-mdm2 allowed efficient translation of an attached reporter gene in the tumor cells. These results are consistent with a model in which overexpression of MDM2 in certain tumors results from a change in mRNA structure due to a switch in promoter usage.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5631-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10523842-5' Untranslated Regions,
pubmed-meshheading:10523842-Cells, Cultured,
pubmed-meshheading:10523842-Choriocarcinoma,
pubmed-meshheading:10523842-Female,
pubmed-meshheading:10523842-Fibroblasts,
pubmed-meshheading:10523842-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10523842-HeLa Cells,
pubmed-meshheading:10523842-Human Growth Hormone,
pubmed-meshheading:10523842-Humans,
pubmed-meshheading:10523842-Lung,
pubmed-meshheading:10523842-Nuclear Proteins,
pubmed-meshheading:10523842-Oncogenes,
pubmed-meshheading:10523842-Open Reading Frames,
pubmed-meshheading:10523842-Promoter Regions, Genetic,
pubmed-meshheading:10523842-Protein Biosynthesis,
pubmed-meshheading:10523842-Proto-Oncogene Proteins,
pubmed-meshheading:10523842-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:10523842-RNA, Messenger,
pubmed-meshheading:10523842-Ribosomes,
pubmed-meshheading:10523842-Tumor Cells, Cultured,
pubmed-meshheading:10523842-Uterine Neoplasms
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pubmed:year |
1999
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pubmed:articleTitle |
Role of two upstream open reading frames in the translational control of oncogene mdm2.
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pubmed:affiliation |
Department of Biochemistry, University of Washington, Seattle, Washington, WA 98195-7350, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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