Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase.

The transcription factor E2F-1 plays a key role in regulating cell cycle progression. Accordingly, E2F-1 activity is itself tightly controlled by a series of transcriptional and post-transcriptional events. Here we show that the E2F-1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F-1 phosphorylation observed in cell extracts and that endogenous E2F-1 interacts in vivo with p62, a component of TFIIH, during S phase. When the two phosphorylation sites in E2F-1 are mutated to alanine, the stability of the E2F-1 activation domain is greatly increased. These results suggest that TFIIH-mediated phosphorylation of E2F-1 plays a role in triggering E2F-1 degradation during S phase.