E2F-6, a member of the E2F family that can behave as a transcriptional repressor

Abstract

The E2F family of proteins is required to establish the correct cell-cycle-dependent transcription of genes that direct the process of cell division. All previously identified E2F proteins can act in a similar manner; depending on whether or not they are associated with the cell cycle inhibitors the retinoblastoma protein (pRB), p107, or p130, they can either repress or activate the transcription of E2F-responsive genes. We now report the cloning and characterization of another E2F family member, E2F-6, whose structure is reminiscent of the dominant inhibitors of other transcription factor families. The dimerization and DNA binding properties of E2F-6 are similar to those of the other E2F family members. However, it is not regulated by pRB, p107, or p130, and it is unable to activate transcription. Instead, it can act to repress the transcription of E2F responsive genes by countering the activity of the other E2F complexes via a pRB-, p107-, or p130-independent mechanism.

Retinoblastoma family genes

“…Consistent with these structural features, this subgroup of E2Fs functions mainly as repressors of E2F target gene expression, and they translocate into the nucleus when in complex with the Rb family of proteins during the G0/G1 phases of the cell cycle (Muller et al, 1997;Verona et al, 1997). E2Fs 6-8, representing the remaining two subgroups, also function as transcriptional repressors (Trimarchi et al, 1998(Trimarchi et al, , 2001de Bruin et al, 2003a;Di Stefano et al, 2003;Attwooll et al, 2004b;Maiti et al, 2005). However, in contrast to E2Fs 1-5, these E2F proteins do not have the Rb-binding sequence at the C-terminus, and therefore their function and regulation are independent of the Rb family of proteins.…”

Life and death decisions by E2F-1

“…7 E2F-6 does not interact with pocket proteins and functions as a negative regulator of E2F-dependent transcription via complexing with chromatin modifiers. [8][9][10] In untransformed cells, the ability of pRb to bind to E2F is regulated by its cell-cycle-dependent phosphorylation. 11 pRb is unphosphorylated during the G0 and early G1 stages of the cell cycle, and this form binds and inhibits E2F (Figure 1).…”

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).…”