E2F-4, a new member of the E2F transcription factor family, interacts with p107.

Abstract

The E2F family of transcription factors has been implicated in the regulation of cell proliferation, and £2F-binding sites are present in the promoters of several growth-regulating genes. E2F family members are functionally regulated, in part, by complex formation with one or more members of the nuclear pocket protein family, RB, pl07, and pl30. Pocket protein regulation of E2F likely contributes to normal cellular growth control. While the three cloned species of E2F, E2F-1, E2F-2, and E2F-3, are known to be targets of RB interaction, no E2F species has yet been shown to be a specific pl07 or pl30 target. Here, we describe the cloning of a new member of the E2F family, E2F-4, which forms heterodimers with a member(s) of the DP family and, unlike some family members, is present throughout the cell cycle and appears to be a differentially phosphorylated pl07-binding partner. pl07 binding not only can be linked to the regulation of E2F-4 transcriptional activity, but also to suppression of the ability of E2F-4 to transform an immortalized rodent cell line.

Cell cycle control and beyond: emerging roles for the retinoblastoma gene family

“…This timed regulation is demonstrated through the complexes formed with the E2F family. In vivo studies demonstrate that Rb2/p130 binds to E2F-4 and -5 in G0 and p107 is associated with E2F-4, especially in G1, whereas Rb/p105 binds to E2F-4 in S phase (Ginsberg et al, 1994;Sardet et al, 1995;Moberg et al, 1996;De Luca et al, 1997;Howard et al, 2000). This sequence is most likely guided by a sequential activation and deactivation of the Rb gene family.…”

E2F-3 accumulation is regulated by polypeptide stability

“…At present the E2F family is known to contain at least ®ve members, the DP family contains two members, and the Rb family contains three members. Heterodimers containing E2F-4 and E2F-5 appear to form trimeric complexes with all three members of the Rb family, whereas E2F-1, -2 and -3 are more selective and interact with pRb alone (Beijersbergen et al, 1994;Dyson et al, 1993;Ginsberg et al, 1994;Hijmans et al, 1995;Ikeda et al, 1996;Lees et al, 1993;Moberg et al, 1996). Recent evidence suggests that it is likely that di erent members of the E2F family may perform distinct functions in an organism.…”

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

“…Particularly noteworthy among these are the interactions with the E2F/DP family of transcription factors (Cao et al, 1992;Devoto et al, 1992;Helin et al, 1992Helin et al, , 1993Kaelin et al, 1992;Shan et al, 1992;Shirodkar et al, 1992;Cobrinik et al, 1993;Ivey-Hoyle et al, 1993;Lees et al, 1993;Bandara et al, 1994;Bejersbergen et al, 1994;Ginsberg et al, 1994;Buck et al, 1995;Hijmans et al, 1995;Ormondroyd et al, 1995;Sardet et al, 1995;Wu et al, 1995;Zhang and Chellappan, 1995). The E2F transcription factors are thought to control expression of a number of genes involved in cell cycle progression (reviewed in Cobrinik, 1996).…”

“…The E2F transcription factors are thought to control expression of a number of genes involved in cell cycle progression (reviewed in Cobrinik, 1996). The interactions between the Rb family members and E2F members e ectively inhibit E2F-mediated transactivation (Hamel et al, 1992;Heibert et al, 1992;Weintraub et al, 1992;Zamanian and LaThangue, 1992;Flemington et al, 1993;Helin et al, 1993;Schwartz et al, 1993;Zamanian and LaThangue, 1993;Zhu et al, 1993;Beijersbergen et al, 1994;Ginsberg et al, 1994;Johnson, 1995;Smith and Nevins, 1995;Vairo et al, 1995). Interactions involving pRB or p107 and various other cellular proteins, including other transcription factors, also have been described (reviewed in Whyte, 1995).…”