title: Residues phosphorylated by TFIIH are required for E2F-1 degradation during S-phase.
abstract: 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.
authors.affiliation: Wellcome/CRC Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
authors.forename: L
authors.initials: L
authors.lastname: Vandel
authors.forename: T
authors.initials: T
authors.lastname: Kouzarides
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D015534:Trans-Activators; D050680:Transcription Factor DP1; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D050680:Transcription Factor DP1; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; D013912:Threonine; D012694:Serine; D011494:Protein Kinases