transcription factor E4F1 (E3 ubiquitin-protein ligase E4F1, E4F transcription factor 1, transcription factor E4F, p120E4F, p50E4F, E4F1, E4F)
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Function
- may function as a transcriptional repressor
- may also function as a ubiquitin ligase mediating ubiquitination of chromatin-associated TP53
- functions in cell survival & proliferation through control of the cell cycle
- functions in the p53 & pRB tumor suppressor pathways & regulates the cyclin CCNA2 transcription
- protein degradation; protein ubiquitination
- proteolytic cleavage produces a 50 kD N-terminal peptide (p50E4F) which has a DNA-binding activity & activates transcription in presence of the adenoviral E1A protein
- the major full length protein (p120E4F) functions as a repressor of transcription
- phosphorylated; p120E4F & p50E4F are both phosphorylated
- phosphorylation is cell cycle-dependent & differentially
- regulates DNA-binding activity & function of both forms may be sumoylated by UBE2I upon interaction with CDKN2A
- forms a complex with CDKN2A & TP53
- interactions with TP53, RB1, ANP32A, BMI1 & FHL2 regulate E4F1 activity
- interacts with HDAC1, HMGA2 & RASSF1
- interacts with HBV protein X
Structure
- homodimer
- binds DNA as a dimer.
- contains 9 C2H2-type Zn+2 fingers
Compartment
- nucleus, nucleoplasm
- a small fraction is detected in the cytoplasm
- excluded from the nucleolus where it is targeted upon CDKN2A overexpression
- localizes to the mitotic spindle during embryogenesis (putative)
Expression
- ubiquitously expressed
- expressed in a variety of fetal tissues
- up-regulated by estrogen
Pathology
- identified as a cellular target of the adenoviral oncoprotein E1A, it is required for both transcriptional activation & repression of viral genes
More general terms
- ligase or synthetase
- transcriptional silencer (transcriptional repressor)
- C2H2 type zinc finger protein