RbAp48 belongs to the histone deacetylase complex that associates with theretinoblastoma protein

The retinoblastoma susceptibility gene product, the Rb protein, is a key re gulator of mammalian cell proliferation. One of the major targets of Rb is the S phase inducing E2F transcription factor. Once bound to E2F, Rb repres ses the expression of E2F-regulated genes. Transcriptional repression by Rb is believed to be crucial for the proper control of cell growth. Recently, we and others showed that Rb represses transcription through the recruitme nt of a histone deacetylase. Interestingly, we show here that the Rb-associ ated histone deacetylase complex could deacetylate polynucleosomal substrat es, indicating that other proteins could be present within this complex. Th e Rb-associated protein RbAp48 belongs to many histone deacetylase complexe s. We show here that the histone deacetylase HDAC1 is able to mediate the f ormation of a ternary complex containing Rb and RbAp48. Moreover, less deac etylase activity was found associated with Rb in cell extracts depleted for RbAp48 containing complexes, demonstrating that Rb, histone deacetylase, a nd RbAp48 are physically associated in live cells. Taken together, these da ta indicate that RbAp48 is a component of the histone deacetylase complex r ecruited by Rb, Finally, we found that E2F1 and RbAp48 are physically assoc iated in the presence of Rb and HDAC1, suggesting that RbAp48 could be invo lved in transcriptional repression of E2F-responsive genes.