Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light. (Article, 1999) [WorldCat.org]
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Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light.
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Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light.

Author: L J Saucedo Affiliation: Program in Cell and Molecular Biology and the Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.; C D Myers; M E Perry
Edition/Format: Article Article : English
Publication:The Journal of biological chemistry, v274 n12 (19990319): 8161-8
Other Databases: WorldCatWorldCat
Summary:
The mdm2 (murine double minute 2) oncogene encodes several proteins, the largest of which (p90) binds to and inactivates the p53 tumor suppressor protein. Multiple MDM2 proteins have been detected in tumors and in cell lines expressing high levels of mdm2 mRNAs. Here we show that one of these proteins (p76) is expressed, along with p90, in wild-type and p53-null mouse embryo fibroblasts, indicating that it may have  Read more...
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Details

Document Type: Article
All Authors / Contributors: L J Saucedo Affiliation: Program in Cell and Molecular Biology and the Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.; C D Myers; M E Perry
ISSN:0021-9258
Language Note: English
Unique Identifier: 119123039
Awards:

Abstract:

The mdm2 (murine double minute 2) oncogene encodes several proteins, the largest of which (p90) binds to and inactivates the p53 tumor suppressor protein. Multiple MDM2 proteins have been detected in tumors and in cell lines expressing high levels of mdm2 mRNAs. Here we show that one of these proteins (p76) is expressed, along with p90, in wild-type and p53-null mouse embryo fibroblasts, indicating that it may have an important physiological role in normal cells. Expression of this protein is induced, as is that of p90, by UV light in a p53-dependent manner. The p76 protein is synthesized via translational initiation at AUG codon 50 and thus lacks the N terminus of p90 and does not bind p53. In cells, p90 and p76 can be synthesized from mdm2 mRNAs transcribed from both the P1 (constitutive) and P2 (p53-responsive) promoters. Site-directed mutagenesis reveals that these RNAs give rise to p76 via internal initiation of translation. In addition, mdm2 mRNAs lacking exon 3 give rise to p76 exclusively, and such mRNAs are induced by p53 in response to UV light. These data indicate that p76 may be an important product of the mdm2 gene and a downstream effector of p53.

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