E2F-6, A MEMBER OF THE E2F FAMILY THAT CAN BEHAVE AS A TRANSCRIPTIONAL REPRESSOR

The E2F family of proteins is required to establish the correct cell-c ycle-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 ge nes. We now report the cloning and characterization of another E2F fam ily member, E2F-6, whose structure is reminiscent of the dominant inhi bitors of other transcription factor families. The dimerization and DN A binding properties of E2F-6 are similar to those of the other E2F fa mily 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 mech anism.