E2F1 phospho T433
Function
Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication (PubMed:10675335, PubMed:12717439, PubMed:17050006, PubMed:17704056, PubMed:18625225, PubMed:28992046). The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase (PubMed:10675335, PubMed:12717439, PubMed:17704056). E2F1 binds preferentially RB1 in a cell-cycle dependent manner (PubMed:10675335, PubMed:12717439, PubMed:17704056). It can mediate both cell proliferation and TP53/p53-dependent apoptosis (PubMed:8170954). Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812). Directly activates transcription of PEG10 (PubMed:17050006, PubMed:18625225, PubMed:28992046). Positively regulates transcription of RRP1B (PubMed:20040599).
Post-translational modifications
Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase (PubMed:12717439, PubMed:7838523). Phosphorylation at Ser-364 by CHEK2 stabilizes E2F1 upon DNA damage and regulates its effect on transcription and apoptosis (PubMed:12717439). Phosphorylation at Ser-403 by GSK3B promotes interaction with USP11, leading to its deubiquitination and stabilization (PubMed:28992046).
Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its degradation (PubMed:28992046). Deubiquitinated by USP11 following phosphorylation by GSK3B, promoting its stability (PubMed:28992046).
Acetylation stimulates DNA-binding. Enhanced under stress conditions such as DNA damage and inhibited by retinoblastoma protein RB1. Regulated by KAP1/TRIM28 which recruits HDAC1 to E2F1 resulting in deacetylation. Acetylated by P/CAF/KAT2B.
Methylation at Lys-185 by SETD7 promotes E2F1 ubiquitin-dependent proteasomal degradation.
Sequence Similarities
Belongs to the E2F/DP family.
Cellular localization
- Nucleus
Alternative names
RBBP3, E2F1, Transcription factor E2F1, E2F-1, PBR3, Retinoblastoma-associated protein 1, Retinoblastoma-binding protein 3, pRB-binding protein E2F-1, RBAP-1, RBBP-3
Database links
Other research areas
- Oncology