HETERODIMERIZATION OF THE TRANSCRIPTION FACTORS E2F-1 AND DP-1 LEADS TO COOPERATIVE TRANSACTIVATION

The E2F transcription factor has been implicated in the regulation of genes whose products are involved in cell proliferation. Two proteins have recently been identified with E2F-like properties. One of these p roteins, E2F-1, has been shown to mediate E2F-dependent trans-activati on and to bind the hypophosphorylated form of the retinoblastoma prote in (pRB). The other protein, murine DP-1, was purified from an E2F DNA -affinity column, and it was subsequently shown to bind the consensus E2F DNA-binding site. To study a possible interaction between E2F-1 an d DP-1, we have now isolated a cDNA for the human homolog of DP-1. Hum an DP-1 and E2F-1 associate both in vivo and in vitro, and this intera ction leads to enhanced binding to E2F DNA-binding sites. The associat ion of E2F-1 and DP-1 leads to cooperative activation of an E2F-respon sive promoter. Finally, we demonstrate that E2F-1 and DP-1 association is required for stable interaction with pRB in vivo and that trans-ac tivation by E2F-1/DP-1 heterodimers is inhibited by pRB. We suggest th at ''E2F'' is the activity that is formed when an E2F-1-related protei n and a DP-1-related protein dimerize.