THE DNAJ DOMAIN OF POLYOMAVIRUS LARGE T-ANTIGEN IS REQUIRED TO REGULATE RB FAMILY TUMOR-SUPPRESSOR FUNCTION

Tumor suppressors of the retinoblastoma susceptibility gene family reg ulate cell growth and differentiation, Polyomavirus large T antigens ( large T) bind Rb family members and block their function, Mutations of large T sequences conserved with the DnaJ family affect large T bindi ng to a cellular DnaK, heat shock protein 70, The same mutations aboli sh large T activation of E2F-containing promoters and Rb binding-depen dent large T activation of cell cycle progression, Cotransfection of a cellular DnaJ domain blocks wild-type large T action, showing that th e connection between the chaperone system and tumor suppressors is dir ect, Although they are inactive in assays dependent on Rb family bindi ng, mutants in the J region retain the ability to associate with pRb, p107, and p130. This suggests that binding of Rb family members by lar ge T is not sufficient for their inactivation and that a functional J domain is required as well, This work connects the DnaJ and DnaK molec ular chaperones to regulation of tumor suppressors by polyomavirus lar ge T.