FUNCTIONAL INTERACTION BETWEEN E2F-4 AND P130 - EVIDENCE FOR DISTINCTMECHANISMS UNDERLYING GROWTH SUPPRESSION BY DIFFERENT RETINOBLASTOMA PROTEIN FAMILY MEMBERS

Little is known of the mechanisms controlling the G(0)/G(1) transition of the cell cycle. The induction of immediate early gene expression, thought to be important for this process, suggests that the key factor s controlling this transition preexist in quiescent cells. The E2F fam ily of transcription factors likely play an important role in this pro cess, because E2F DNA-binding activity exists in quiescent cells, and the induction of at least some immediate early genes requires intact E 2F regulatory promoter sites. Here, we show that the major G(0) E2F ac tivity of primary human T cells, E2F-4, is stably bound to the p130 po cket protein in association with a DP heterodimerization partner. p130 -E2F-4 binding has functional implications because p130 effectively su ppressed E2F-4-mediated trans-activation, and coexpression of E2F-4 ov ercame p130-mediated G(1) arrest more efficiently than RB-induced G(1) blockade. Conversely, E2F-1 overrode an RB-induced G(1) block more ef ficiently than E2F-4. Thus, p130 and RB appear to induce cell cycle ar rest via biochemically distinct mechanisms that involve different E2F family members.