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Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: Transforming ability and frequent detection in human cancer

Lookup NU author(s): Professor Alan Calvert, Dr John Anderson, Professor David Neal, Professor John LunecORCiD


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The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave loci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.

Publication metadata

Author(s): Sigalas, I., Calvert, A.H., Anderson, J.J., Neal, D.E., Lunec, J.

Publication type: Article

Publication status: Published

Journal: Nature Medicine

Year: 1996

Volume: 2

Issue: 8

Pages: 912-917

Print publication date: 01/01/1996

ISSN (print): 1078-8956

ISSN (electronic): 1546-170X


DOI: 10.1038/nm0896-912

PubMed id: 8705862


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