RETINOBLASTOMA PROTEIN REPRESSES TRANSCRIPTION BY RECRUITING A HISTONE DEACETYLASE

The retinoblastoma tumour-suppressor protein Rb-1 inhibits cell prolif eration by repressing a subset of genes that are controlled by the E2F family of transcription factors(2) and which are involved in progress ion from the G1 to the S phase of the cell cycle, Rb, which is recruit ed to target promoters by E2F1 (ref. 3), represses transcription by ma sking the E2F1 transactivation domain(4) and by inhibiting surrounding enhancer elements(5-8), an active repression that could be crucial fo r the proper control of progression through the cell cycle(9). Some tr anscriptional regulators act by acetylating or deacetylating the tails protruding from the core histones(10), thereby modulating the local s tructure of chromatin: for example, some transcriptional repressors fu nction through the recruitment of histone deacetylases(11). We show he re that the histone deacetylase HDAC1 physically interacts and coopera tes with Rb, In HDAC1, the sequence involved is an LXCXE motif, simila r to that used by viral transforming proteins to contact Rb, Our resul ts strongly suggest that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a lik ely target for transforming viruses.