E2F-4 AND E2F-5, 2 MEMBERS OF THE E2F FAMILY, ARE EXPRESSED IN THE EARLY PHASES OF THE CELL-CYCLE

The E2F transcription factors play a role in regulating the expression of genes required for cell proliferation, Their activity appears to b e regulated by association with the retinoblastoma protein (pRb) and t he pRb-related proteins p107 and p130. In vivo, pRb is found in comple x with a subset of E2F components-namely, E2F-1, E2F-2, and E2F-3. Wer e we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to interact with p130 in a yeast two-hybrid system. E2F-4 and -5 shar e common sequences with E2F-1, E2F-2, and E2F-3 and, like these other E2Fs, the ability to heterodimerize with DP-1, thereby acquiring the a bility to bind an E2F DNA recognition sequence with high affinity. How ever, in contrast to E2F-1, E2F-4 and E2F-5 fail to bind pRb in a two- hybrid assay. Moreover, they show a unique pattern of expression in sy nchronized human keratinocytes: E2F-4 and E2F-5 mRNA expression is max imal in mid-G(1) phase before E2F-1 expression is detectable. These fi ndings suggest that E2F-4 and E2F-5 may contribute to the regulation o f early G(1) events including the G(0)/G(1) transition.