THE RETINOBLASTOMA PROTEIN AND BRG1 FORM A COMPLEX AND COOPERATE TO INDUCE CELL-CYCLE ARREST

The retinoblastoma tumor suppressor protein (RB) binds several cellula r proteins involved in cell cycle progression. Using the yeast two-hyb rid system, we found that RB bound specifically to the protein BRG1. B RG1 shares extensive sequence similarity to Drosophila brahma, an acti vator of homeotic gene expression, and the yeast transcriptional activ ator SNF2/SWI2. BRG1 contains an RB-binding motif found in viral oncop roteins and bound to the A/B pocket and the hypophosphorylated form of RB. BRG1 did not bind RB in viral oncoprotein-transformed cells. Coim munoprecipitation experiments suggested BRG1 associates with the RB fa mily in vivo. In the human carcinoma cell line SW13, BRG1 exhibited tu mor suppressor activity by inducing formation of flat, growth-arrested cells. This activity depended on the ability of BRG1 to cooperate and complex with RB, as both an RB-nonbinding mutant of BRG1 and the sequ estration of RB by adenovirus E1A protein abolished flat cell formatio n.