Analysis of molecular interactions of the p53-family p51(p63) gene products in a yeast two-hybrid system: Homotypic and heterotypic interactions and association with p53-regulatory factors

p51 in the p53 tumor suppressor family, also referred to as p63, encodes mu ltiple isoforms including p51A (TAp63 gamma) and p51B (TAp63 alpha). The p5 3 protein forms a tetramer, and its stability and activity are regulated by molecular association with viral and cellular proteins and by biochemical modifications. Using a yeast two-hybrid system, the p51A and p51B isoforms were examined for homotypic and heterotypic interactions in the p53 family proteins and for their affinity to the p53-regulatory factors. Results indi cate a homotypic interaction dependent on the presumed oligomerization doma in of the p51 proteins. The possibility of a weak heterotypic interaction b etween p51 and p73 proteins was suggested, while association between p51 an d p53 appeared improbable. Furthermore, unlike p53, the p51 proteins failed to display an affinity to SV40 large T antigen or MDM2-family proteins. Ha ving several features in common with p53, the p51 proteins may function in biological processes apart from p53. (C) 2001 Academic Press.