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Regulation of E2F1 activity by acetylation.

The EMBO journal | Feb 15, 2000

http://www.ncbi.nlm.nih.gov/pubmed/10675335

During the G(1) phase of the cell cycle, an E2F-RB complex represses transcription, via the recruitment of histone deacetylase activity. Phosphorylation of RB at the G(1)/S boundary generates a pool of 'free' E2F, which then stimulates transcription of S-phase genes. Given that E2F1 activity is stimulated by p300/CBP acetylase and repressed by an RB-associated deacetylase, we asked if E2F1 was subject to modification by acetylation. We show that the p300/CBP-associated factor P/CAF, and to a lesser extent p300/CBP itself, can acetylate E2F1 in vitro and that intracellular E2F1 is acetylated. The acetylation sites lie adjacent to the E2F1 DNA-binding domain and involve lysine residues highly conserved in E2F1, 2 and 3. Acetylation by P/CAF has three functional consequences on E2F1 activity: increased DNA-binding ability, activation potential and protein half-life. These results suggest that acetylation stimulates the functions of the non-RB bound 'free' form of E2F1. Consistent with this, we find that the RB-associated histone deacetylase can deacetylate E2F1. These results identify acetylation as a novel regulatory modification that stimulates E2F1's activation functions.

Pubmed ID: 10675335 RIS Download

Mesh terms: Acetylation | Acetyltransferases | Amino Acid Sequence | Animals | Base Sequence | Binding Sites | Carrier Proteins | Cell Cycle Proteins | Cell Line | DNA | DNA-Binding Proteins | E2F Transcription Factors | E2F1 Transcription Factor | G1 Phase | Histone Acetyltransferases | Histone Deacetylases | Humans | In Vitro Techniques | Molecular Sequence Data | Mutagenesis, Site-Directed | Nuclear Proteins | Retinoblastoma Protein | Retinoblastoma-Binding Protein 1 | S Phase | Sequence Homology, Amino Acid | Trans-Activators | Transcription Factor DP1 | Transcription Factors | Transcriptional Activation | p300-CBP Transcription Factors