Reactome | Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex

Stable Identifier

R-HSA-1226095

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex

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In late G1, cyclin D dependent kinases CDK4 and CDK6 phosphorylate RBL1 (p107) on four serine and threonine residues (S964, S975, T369 and S640), leading to dissociation of phosphorylated RBL1 (p107) from E2F4 in complex with either DP-1 or DP-2. E2F4, which lacks nuclear localization signal, is then thought to translocate to the cytosol, allowing E2F promoter sites to become occupied by activating E2Fs (E2F1, E2F2, and E2F3), resulting in transcription of E2F targets needed for cell cycle progression.

Literature References

PubMed ID	Title	Journal	Year
7797074	Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes Kerkhoven, RM, Carlée, L, Beijersbergen, RL, Bernards, R	Genes Dev	1995
9144196	The subcellular localization of E2F-4 is cell-cycle dependent Livingston, DM, Gaubatz, S, Lindeman, GJ, Ginsberg, D	Proc Natl Acad Sci U S A	1997
11884610	Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4 Leng, X, Adams, PD, Noble, M, Qin, J, Harper, JW	Mol Cell Biol	2002

Participants

Input

Output

Participates

as an event of

Cyclin D associated events in G1 (Homo sapiens)

Catalyst Activity

cyclin-dependent protein serine/threonine kinase activity of p-T172-CDK4,p-T177-CDK6:CCND:CDKN1A,CDKN1B,(CDKN1C); p-T172-CDK4,p-T177-CDK6:CCND; (p-T172-CDK4,p-T177-CDK6:CCND:p-Y88-CDKN1B) [nucleoplasm]

Physical Entity

p-T172-CDK4,p-T177-CDK6:CCND:CDKN1A,CDKN1B,(CDKN1C); p-T172-CDK4,p-T177-CDK6:CCND; (p-T172-CDK4,p-T177-CDK6:CCND:p-Y88-CDKN1B) [nucleoplasm] (Homo sapiens)

Activity

cyclin-dependent protein serine/threonine kinase activity (GO:0004693)

Orthologous Events

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Bos taurus)

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Canis familiaris)

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Drosophila melanogaster)

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Gallus gallus)

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Mus musculus)

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Rattus norvegicus)

Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex (Sus scrofa)