The E2F family of transcription factors has been implicated in the reg
ulation of cell proliferation, and E2F-binding sites are present in th
e promoters of several growth-regulating genes. E2F family members are
functionally regulated, in part, by complex formation with one or mor
e members of the nuclear pocket protein family, RB, p107, and p130. Po
cket protein regulation of E2F likely contributes to normal cellular g
rowth control. While the three cloned species of E2F, E2F-1, E2F-2, an
d E2F-3, are known to be targets of RB interaction, no E2F species has
yet been shown to be a specific p107 or p130 target. Here, we describ
e the cloning of a new member of the E2F family, E2F-4, which forms he
terodimers with a member(s) of the DP family and, unlike some family m
embers, is present throughout the cell cycle and appears to be a diffe
rentially phosphorylated p107-binding partner. p107 binding not only c
an be linked to the regulation of E2F-4 transcriptional activity, but
also to suppression of the ability of E2F-4 to transform an immortaliz
ed rodent cell line.