retinoblastoma-binding protein related to a negative regulator of Ras in yeast

The growth suppression function of the retinoblastoma protein (Rb) is thought to be mediated by Rb binding to cellular proteins p48 is one of the major proteins that binds to a putative functional domain at the carboxy terminus of the Rb protein. Here we report the isolation of a full-length complementary DNA (RbAp4g) encoding p48. Complex formation between p48 and Rb occurs in vitro and in vivo, and apparently involves direct interaction between the proteins. Like Rb, p48 is a ubiquitously expressed nuclear protein. RbAp4g share sequence homology with MSI1, a negative regulator of the Ras-cyclic AMP pathway in the yeast Saccharomyces cerevisiae. Furthermore, like MSI1, human RbAp48 suppresses the heat-shock sensitivity of the yeast ira1 strains and RAS2(Val19) strains. Interaction with p48 may be one of the mechanisms for suppression of growth mediated by Rb.