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MBP1: a novel mutant p53-specific protein partner with oncogenic properties

Oncogene volume 18, pages 3608–3616 (1999)Cite this article

Abstract

Using a yeast two-hybrid screening strategy with a common tumour-derived p53 mutant as bait, we identified several mutant p53-interacting partners including the known proteins wild-type (wt) p53, hUBC9 and GBP/PIAS1. In addition, a novel protein partner was identified which we have termed MBP1, for Mutant p53-Binding Protein 1. MBP1 is a new member of the emerging fibulin gene family, which currently comprises fibulin-1, fibulin-2 and S1-5. Expression of MBP1 mRNA is differentially regulated both temporally during development of the mouse embryo and in a tissue-specific manner within the adult. Specific interaction between MBP1 and mutant p53 was illustrated by both two-hybrid analysis in yeast and co-immunoprecipitation in mammalian cells. MBP1 displayed the following order of binding specificity towards different p53 forms: H175 >G281>H273 ⩾W248>wt p53. Thus, MBP1 appears to bind preferentially to p53 mutants of the `structural' rather than `contact' class, reflecting a potential bias towards those mutants having a significant alteration in conformation from that assumed by wt p53. We propose that MBP1 is the product of a candidate oncogene as rates of both neoplastic transformation and tumour cell growth were shown to be significantly enhanced when the protein is ectopically overexpressed. Furthermore, MBP1 may play a role in determining if a `gain of function' effect is seen with certain p53 mutants.

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Acknowledgements

The work of WM Gallagher is supported by a Marie Curie Research Training Grant (category B30) under the framework of the European Commission's BIOTECH2 program. We would like to thank Dr PM Chevray for the generous donation of the yeast two-hybrid expression plasmids, and Mr F Lacroix for provision of the rat embryos. The authors also wish to acknowledge Dr F Lavelle, Dr I Barlat and Dr C Marcireau for their advice and expertise.

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Authors and Affiliations

  1. Oncology Department, Rhône-Poulenc Rorer, CRVA, 13 quai Jules Guesde - BP14, 94403, Vitry-sur-Seine Cedex, France

    William M Gallagher, Véronique Sierra, Laurent Debussche & Emmanuel Conseiller

  2. IGBMC, 1 rue Laurent Fries, 67404, Illkirch Cedex, France

    Manuela Argentini

  3. ExonHit Therapeutics, 63/65 Boulevard Massena, 75013, Paris, France

    Laurent Bracco

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  1. William M Gallagher
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Gallagher, W., Argentini, M., Sierra, V. et al. MBP1: a novel mutant p53-specific protein partner with oncogenic properties. Oncogene 18, 3608–3616 (1999). https://doi.org/10.1038/sj.onc.1202937

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