Authors:
I Sigalas, AH Calvert, JJ Anderson, DE Neal, J Lunec
Journal name: 
Nat Med
Citation info: 
2(8):912-917
Abstract: 
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 foci 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.
DOI: 
http://doi.org/10.1038/nm0896-912
E-pub date: 
31 Aug 1996
Users with this publication listed: 
David Neal