INTERACTION OF THE PRB-FAMILY PROTEINS WITH FACTORS CONTAINING PAIRED-LIKE HOMEODOMAINS

The specific loss of pRB or p107 together with p130 disrupts the norma l development of only a very limited spectrum of tissues. These develo pmental defects have been attributed primarily to deregulation of E2F activity and consequent uncontrolled proliferation. We hypothesized, h owever, that the tissue-specific nature of these defects may also refl ect deregulation of pRB-family associated factors that are specificall y involved in determining cell fate. We report here that the pRB-famil y members interact with transcription factors which contain paired-lik e homeodomains such as MHox, Chx10 and Pax-3. The interaction between the pRB-family and the paired-like homeodomain proteins was initially identified in a yeast two-hybrid screen where the N-terminal portion o f p130 was used to isolate interacting factors from an embryonic mouse library. This interaction was confirmed by in vitro binding and co-im munoprecipitation assays. We show further that coexpression of Pax-3 d ependent pRB, p107 or p130 with Pax-3 causes repression of activated t ranscription from the c-met promoter. These data demonstrate that the pRB-family proteins can modulate the activity of factors which specifi cally control cell fate and/or differentiation as well as controlling cell cycle regulators.