Reactome | RB1 binds and inhibits E2F1/2/3:DP1/2 complexes

RB1 binds and inhibits E2F1/2/3:DP1/2 complexes

Stable Identifier

R-HSA-9018017

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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RB1 binds and inhibits E2F1/2/3:DP1/2 complexes

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RB1 tumor suppressor, the product of the retinoblastoma susceptibility gene, binds to E2F transcription factors E2F1, E2F2 and E2F3, presumably heterodimerized with TFDP1 or TFDP2. The interaction involves the pocket domain of RB1. RB1 binding inhibits transcriptional activity of E2F1/2/3:TFDP1/2 complexes, resulting in prevention of G1/S transition (Chellappan et al. 1991, Bagchi et al. 1991, Chittenden et al. 1991, Lees et al. 1993, Hiebert 1993, Wu et al. 2001). Once RB1 is phosphorylated on serine residue S795 by Cyclin D:CDK4/6 complexes, it can no longer associate with and inhibit E2F1/2/3:TFDP1/2 complexes. Thus, CDK4/6-mediated phosphorylation of RB1 leads to transcriptional activation of E2F1/2/3 target genes needed for the S phase of the cell cycle (Connell-Crowley et al. 1997).

Literature References

PubMed ID	Title	Journal	Year
8497257	Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression Hiebert, SW	Mol. Cell. Biol.	1993
11719808	The E2F1-3 transcription factors are essential for cellular proliferation Wu, L, Timmers, C, Maiti, B, Saavedra, HI, Sang, L, Chong, GT, Nuckolls, F, Giangrande, P, Wright, FA, Field, SJ, Greenberg, ME, Orkin, S, Nevins, JR, Robinson, ML, Leone, G	Nature	2001
1828394	The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein Chittenden, T, Livingston, DM, Kaelin, WG	Cell	1991
9190208	Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation Connell-Crowley, L, Harper, JW, Goodrich, DW	Mol Biol Cell	1997
1828393	The retinoblastoma protein copurifies with E2F-I, an E1A-regulated inhibitor of the transcription factor E2F Bagchi, S, Weinmann, R, Raychaudhuri, P	Cell	1991
8246996	The retinoblastoma protein binds to a family of E2F transcription factors Lees, JA, Saito, M, Vidal, M, Valentine, M, Look, T, Harlow, E, Dyson, N, Helin, K	Mol. Cell. Biol.	1993
1828392	The E2F transcription factor is a cellular target for the RB protein Chellappan, SP, Hiebert, S, Mudryj, M, Horowitz, JM, Nevins, JR	Cell	1991