title: MBP1: a novel mutant p53-specific protein partner with oncogenic properties.
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 > or = 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.
authors.affiliation: Oncology Department, Rhône-Poulenc Rorer, CRVA, Vitry-sur-Seine, France.
authors.forename: W M
authors.initials: WM
authors.lastname: Gallagher
authors.forename: M
authors.initials: M
authors.lastname: Argentini
authors.forename: V
authors.initials: V
authors.lastname: Sierra
authors.forename: L
authors.initials: L
authors.lastname: Bracco
authors.forename: L
authors.initials: L
authors.lastname: Debussche
authors.forename: E
authors.initials: E
authors.lastname: Conseiller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D011487:Protein Conformation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C403672:EFEMP2 protein, human; C485883:Efemp2 protein, mouse; D016326:Extracellular Matrix Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C060820:fibulin