AbstractThe product of the retinoblastoma gene (RB1) is believed to function as a negative regulator of cell growth. Recent experimental results suggest that RB1 may exert its growth‐suppressing activity by regulating the transcription of a variety of growth‐related genes, including FOS, MYC, and TGFB1. A series of biochemical and molecular analyses suggest that RB1 indirectly affects gene expression via cell‐cycle‐regulated interactions with transcription factors, such as E2F and SP1. Determination of the mechanisms regulating such protein‐protein interactions and the identification of additional targets of RB1 function will provide vital insights into the role of this tumor‐suppressor gene in mammalian cell proliferation. © 1993 Wiley‐Liss, Inc.