Author: ["Iakovos Sigalas","A. Hilary Calvert","John J. Anderson","David E. Neal","John Lunec"]
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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 carboxy–terminal zinc–finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.Cite this article
Sigalas, I., Calvert, A., Anderson, J. et al. Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: Transforming ability and frequent detection in human cancer. Nat Med 2, 912–917 (1996). https://doi.org/10.1038/nm0896-912 