The mammalian transcription factor E2F plays an important role in regu
lating the expression of genes that are required for passage through t
he cell cycle. This transcriptional activity is inhibited by associati
on with the retinoblastoma tumor suppressor protein (pRB) or its relat
ives p107 and p130. The first cDNA from the E2F family to be cloned wa
s designated E2F-1, and multiple E2F family members have now been iden
tified. They bind to DNA as heterodimers, interacting with proteins kn
own as DP. Here we demonstrate that DP is also a family of polypeptide
s with at least two members (hDP-1 and hDP-2). Both hDP-1 and hDP-2 bi
nd to all E2F family members in vivo, and each complex is capable of a
ctivating transcription. However, the various E2F/DP complexes display
strong differences in the ability to bind to either pRB or p107 in vi
vo, and the specificity of PRE or p107 binding is mediated by the E2F
subunit.