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A novel exon within the mdm2 gene modulates translation initiation in vitro and disrupts the p53-binding domain of mdm2 protein

Oncogene volume 18, pages 7026–7033 (1999)Cite this article

Abstract

The mdm2 protein interacts with a number of proteins involved in cell growth control. Such interactions favour cell proliferation and may explain the oncogenic potential of mdm2 when over-expressed in cells. Interaction with the tumour suppressor p53 involves the N-terminus of mdm2 and targets p53 for rapid degradation by the ubiquitin pathway. We now describe a novel, highly conserved exon of mdm2 (exon α) which includes an in-frame UGA stop codon. Expression of exon α disrupts in vitro translation of the p53 binding domain of mdm2. We propose that exon α induces translation re-initiation at an internal AUG codon within the mdm2α mRNA isoform. The putative mdm2α protein lacks the N-terminus of mdm2 and shows little, if any, binding capacity for p53. Mdm2α mRNA is expressed in a tissue-specific manner and is observed predominantly in testis and peripheral blood lymphocytes. We propose that mdm2α expression may provide a mechanism for uncoupling mdm2-p53 interaction in certain cell types and/or under specific conditions of cell growth.

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Acknowledgements

We thank Arnold Levine and Stephen Picksley for making available the anti-mdm2 antibodies 4B2, 3G5, 2A9, 2A10, and 4B11. We are also indebted to Andrei Okorokov and Ming Jiang, YCR p53 Research Group, for many helpful discussions. Photographic work was prepared by Meg Stark. This work was supported by a grant from Yorkshire Cancer Research to J Milner.

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  1. Department of Biology, YCR P53 Research Group, University of York, York, YO10 5DD, UK

    Nik Veldhoen & Jo Milner

  2. Department of Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, UK

    Su Metcalfe

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Veldhoen, N., Metcalfe, S. & Milner, J. A novel exon within the mdm2 gene modulates translation initiation in vitro and disrupts the p53-binding domain of mdm2 protein. Oncogene 18, 7026–7033 (1999). https://doi.org/10.1038/sj.onc.1203182

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