E2F-INDEPENDENT TRANSCRIPTIONAL REPRESSION BY P107, A MEMBER OF THE RETINOBLASTOMA FAMILY OF PROTEINS

The Rb family of proteins includes pRb, p107, and p130. These nuclear polypeptides associate with cyclins and transcription factors involved in the control of cell proliferation. This has suggested that members of the pRb family may modulate cell growth, at least in part, by regu lating gene transcription. We have investigated the ability of p107 to modulate transcription and compared it with that of pRb. Whereas pRb inhibition of the c-myc promoter required the presence of E2F sites, p 107 inhibition did not. Moreover, p107, but not pRb, repressed transcr iption from other promoters including fibronectin, herpes virus thymid ine kinase, and a synthetic promoter containing a SV40 repeat activato r motif upstream from the adenovirus major late-promoter TATA box. In contrast, the activity of the TATA-lacking promoters from the epiderma l growth factor receptor and the cytoplasmic phospholipase A2 genes wa s unaffected by either p107 or pRb. Likewise, overexpression of p107 o r pRb had no effect on the activity of a synthetic promoter lacking a TATA box and containing the SV40 repeat motif upstream from the termin al transferase gene initiator element. The domains in p107 required fo r transcriptional repression included the A segment of the pocket regi on and parts of the B segment, but not the spacer domain. In spite of their structural similarities, p107 and pRb may contribute to the cont rol of cell proliferation by modulating the transcription of different genes.