A new component of the transcription factor DRTF1/E2F

Abstract

Transcription factor DRTF1/E2F coordinates events in the cell cycle with transcription by its cyclical interactions with important regulators of cellular proliferation like the retinoblastoma tumour-suppressor gene product (Rb) and the Rb-related protein, p107 (refs 1-8). DRTF1/E2F binding sites occur in the control regions of genes involved in proliferation, and both Rb and p107 repress the capacity of DRTF1/E2F to activate transcription (refs 11, 12; M. Zamanian and N.B.L.T., manuscript submitted). Mutant Rb proteins isolated from tumour cells are unable to bind DRTF1/E2F (refs 11-13), and certain viral oncoproteins, such as adenovirus E1A, sequester Rb and p107 in order to free active DRTF1/E2F (refs 5, 11, 12, 14, 15). Here we report the isolation of a complementary DNA encoding DRTF1-polypeptide-1 (DP-1), a major sequence-specific binding protein that is present in DRTF1/E2F, including Rb- and p107-associated DRTF1/E2F. The DNA-binding domain of DP-1 contains a region that resembles that of E2F-1 (refs 16, 17), and recognizes the same sequence. DRTF1/E2F thus appears to contain at least two sequence-specific DNA-binding proteins.

Functional interplay between p53 and E2F through co-activator p300

“…The DP-1 cDNA sequence (Girling et al, 1993) in frame was introduced into pCMV-HA to generate an expression plasmid encoding an amino-terminal HA-tagged full-length DP-1.…”

“…The NdeI and XbaI fragment from pCMV-E2F1 was fused inframe into pCMV-GAD to make the pCMV-GAD/E2F1. To construct pG4-p300 (611 ± 2284), the NdeI fragment from pCMV-p300 was fused in-frame to the Gal4 DNA binding domain sequence of pG4m-polyII vector (Bandara et al, 1993). pCMV-E2F-1D413 was made by internal deletion from pCMV-E2F1.…”

E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes

“…Downregulation of expression of the transcription factor and key cell cycle regulator, E2F, is an early event in normal squamous di erentiation (Saunders et al, 1993b). There are currently six known members of the E2F family in humans, E2F-1 to E2F-6 (Kaelin et al, 1992;Shan et al, 1992;Helin et al, 1992;Lees et al, 1993;Ivey-Hoyle et al, 1993;Beijersbergen et al, 1994;Ginsberg et al, 1994;Itoh et al, 1995;Buck et al, 1995;Gaubatz et al, 1998;Trimarchi et al, 1998;Cartwright et al, 1998), which associate with one of two dimerization partners (DP1 and DP2) (Girling et al, 1993;Rogers et al, 1996) to increase the activity of E2F bound to the promoter region of E2F responsive genes. E2F-1 is the best characterized of the family, with evidence implicating it as a key regulator of G1/S phase traverse (Johnson and Schneider-Broussard, 1998;Yee et al, 1998).…”

A functionally distinct member of the DP family of E2F subunits

“…DP subunits are heterodimeric partner proteins for E2F subunits. The first member to be characterized, DP-1, is a widespread component of physiological E2F activity (Girling et al, 1993;Bandara et al, 1994). It is an essential gene because DP-1 À/À mice exhibit embryonic lethality, in part owing to defective extra-embryonic tissue development (Kohn et al, 2003(Kohn et al, , 2004.…”