E2F DNA binding sites are found in a number of genes whose expression
is tightly regulated during the cell cycle, The activity of E2F transc
ription factors is regulated by association with specific repressor mo
lecules that can bind and inhibit the E2F transactivation domain, For
E2F-1, E2F-2, and E2F-3, the repressor is the product of the retinobla
stoma gene, pRb, E2F-4 interacts with pRb-related p107 and not with pR
b itself, Recently, a cDNA encoding a third member of the retinoblasto
ma gene family, p130, was isolated, p130 also interacts with E2F DNA b
inding activity, primarily in the G(0) phase of the cell cycle, We rep
ort here the cloning of a fifth member of the E2F gene family, The hum
an E2F-5 cDNA encodes a 346-amino-acid protein with a predicted molecu
lar mass of 38 kDa. E2F-5 is more closely related to E2F-4 (78% simila
rity) than to E2F-1 (57% similarity), E2F-5 resembles the other E2Fs i
n that it binds to a consensus E2F site in a cooperative fashion with
DP-1. By using a specific E2F-5 antiserum, we found that under physiol
ogical conditions, E2F-5 interacts preferentially with p130.