Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Regulation of E2F1 activity by acetylation.

The EMBO journal | Feb 15, 2000

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