RB INTERACTS WITH TAF(II)250 TFIID THROUGH MULTIPLE DOMAINS/

The retinoblastoma tumor suppressor gene product (Rb) binds directly t o the largest TFIID subunit, TATA-binding protein associated factor TA F(II)250, first identified as the cell cycle regulatory protein CCG1. Here we map the domains in Rb and TAF(II)250 important for their inter action in vitro and in vivo. Both the amino terminus and the large poc ket of Rb are able to associate independently with TAF(II)250. The bin ding domain(s) within the large pocket are distinct from the viral onc oprotein and E2F binding region since certain pocket mutations, which abolish E1A binding, do not abolish TAF(II)250 binding. Consistent wit h the large pocket of Rb binding to TAF(II)250, the large pocket domai ns of both p107 and p130 are able to bind to TAF(II)250 in vivo. We al so demonstrate that at least two regions of TAF(II)250 are able to bin d to the large pocket of Rb independently whereas the amino terminus o f Rb binds to a distinct domain in TAF(II)250. We further demonstrate that Rb can bind to TFIID in vitro, presumably in part through an inte raction with TAF(II)250. Our results suggest a complex interaction bet ween Rb and TAF(II)250 and imply that TAF(II)250, TFIID, and potential ly other basal transcription factors are targets for regulation by Rb and Rb-related proteins.