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E2F

E2F family of heterodimeric transcription factors originally identified through its role in transcriptional activation of the adenovirus E2 promoter [4] Function: - E2F forms a DNA-binding complex with DP-1 (DRTF1) & binds DNA through the E2 recognition site, 5'-TTTC[CG]CGC-3' - E2F binds to Rb protein [3] - cyclin-dependent kinase (CDK)-mediated phosphorylation of Rb dissociates the Rb-E2F complex, freeing E2F to facilitate transcription of S-phase specific genes [3] Structure: - E2F family of heterodimeric transcription factors E2F1, E2F2, E2F3 & presumably E2F4 all contain a DNA-binding-domain in the central part of the molecule & C-terminal Rb-binding domain Pathology: - viral oncoproteins, notably E1A, T-antigen & HPV E7, are capable of sequestering RB protein, thus releasing active E2F complexes - E2F binds to & activates the adenovirus E2 promoter [4]

Interactions

molecular events

Related

DRTF1/E2F (DP1/E2F) E2 recognition site

Specific

transcription factor E2F1; E2F-1; PBR3; PRB-binding protein E2F-1; retinoblastoma-associated protein 1; RBAP-1; retinoblastoma-binding protein 3; RBBP-3 (E2F1, RBBP3) transcription factor E2F2 (E2F-2, E2F2) transcription factor E2F3 (E2F-3, E2F3, KIAA0075) transcription factor E2F4 (E2F-4, E2F4) transcription factor E2F5 (E2F-5, E2F5) transcription factor E2F6 (E2F-6, E2F6) transcription factor E2F8 (E2F-8, E2F8)

General

immediate early activator phosphoprotein

Figures/Diagrams

Figures/diagrams/slides/tables related to E2F

Properties

COMPARTMENT: cell nucleus MOTIF: binding site SITE: N-TERMINAL FOR-BINDING-OF: CDK2/cyclin A complex domain {CENTRAL} MOTIF: DNA-binding motif binding site FOR-BINDING-OF: transcription factor DP-1 phosphorylation site binding site SITE: C-TERMINAL FOR-BINDING-OF: retinoblastoma-associated protein

References

  1. Mudryj M, Hiebert SW, Nevins JR. A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. EMBO J. 1990 Jul;9(7):2179-84. PMID: 2141565
  2. Xu M, Sheppard KA, Peng CY, Yee AS, Piwnica-Worms H. Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. Mol Cell Biol. 1994 Dec;14(12):8420-31. PMID: 7969176
  3. Enoch T, Norbury C. Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles of p53 and ATM. Trends Biochem Sci. 1995 Oct;20(10):426-30. Review. PMID: 8533157
  4. Cordon-Cardo C. Mutations of cell cycle regulators. Biological and clinical implications for human neoplasia. Am J Pathol. 1995 Sep;147(3):545-60. Review. PMID: 7677168

Component-of

molecular complex