Protein stabilization: a common consequence of mutations in independently derived v-Myc alleles.

Gavine, P. R., Neil, J.C. and Crouch, D. H. (1999) Protein stabilization: a common consequence of mutations in independently derived v-Myc alleles. Oncogene, 18(52), pp. 7552-7558. (doi: 10.1038/sj.onc.1203102) (PMID:10602514)

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Myc is overexpressed in many cancers as a result of gene rearrangement or amplification, but coding sequence changes which cluster in the N-terminal transactivation domain also appear to play a role in tumour progression. The prototypic v-Myc gene of MC29 virus differs from avian c-Myc by a series of mutations, including a change at a regulatory phosphorylation site within the mutational hotspot (thr-61) which is known to potentiate transformation in vitro. We now show that the mutation at thr-61 stabilizes the v-Myc protein (turnover difference) and that this single mutation is both necessary and sufficient for the phenotype. A major involvement of the proteasome in Myc degradation was confirmed, but surprisingly, a dilysine motif adjacent to thr-61 proved not to be the ubiquitin target. Two other v-Myc genes which carry a mutation at thr-61 (avian MH2) or a large deletion encompassing this domain (feline T17) were found to be stabilized to a similar extent as MC29, showing that stabilization is a common feature of independently derived Myc oncogenes. These results suggest a common selective process in the genesis of these three viral oncoproteins and a mechanistic link with Jun, Fos and Myb oncoproteins which are also stabilized relative to their cellular counterparts.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Neil, Professor James
Authors: Gavine, P. R., Neil, J.C., and Crouch, D. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN (Online):1476-5594

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