transcription factor E2F4 (E2F-4, E2F4)
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Function
- transcription activator
- 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
- the DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase
- E2F4 binds with high affinity to RBL1 & RBL2
- in some instances, can also bind RB protein
- component of the DRTF1/E2F transcription factor complex
- binds cooperatively with DP-1 to E2F sites
- the E2F4/DP-1 dimer interacts preferentially with pocket protein RBL1, which inhibits the E2F transactivation domain
- lower affinity interaction has been found with retinoblastoma protein RB1
- interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation
- interacts with HCFC1
- component of the DREAM complex composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBBP4, RBL2, TFDP1 & TFDP2
- the complex exists in quiescent cells where it represses cell cycle-dependent genes
- dissociates in S phase when LIN9, LIN37, LIN52 & LIN54 form a subcomplex that binds to MYBL2
- differentially phosphorylated in vivo
Structure
- DNA-binding-domain in the central part of the molecule
- C-terminal Rb-binding domain
- belongs to the E2F/DP family
Compartment
Expression
- found in all tissue examined including heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
- present in the growth-arrested state, its abundance does not change significantly as cells move into & through the cell cycle
Polymorphism
- the poly-Ser region of E2F4 is polymorphic & the number of Ser varies in the population (from 8 to 17)
- variation might be associated with tumorigenesis