Reactome | Association of INK4 family proteins with CDK4/6

Association of INK4 family proteins with CDK4/6

Stable Identifier

R-HSA-182594

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Association of INK4 family proteins with CDK4/6

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Prior to mitogen activation, the inhibitory proteins of the INK4 family (p15, p16, p18, and p19) associate with the catalytic domains of free CDK4 and CDK6, preventing their association with D type cyclins (CCND1, CCND2 and CCND3), and thus their activation and their inhibitory phosphorylation of the RB family (Serrano et al. 1993, Hannon and Beach 1994, Guan et al. 1994, Guan et al. 1996, Parry et al. 1995). Inactivation and defects of RB1 strongly upregulate p16INK4A (Parry et al. 1995).

Literature References

PubMed ID	Title	Journal	Year
8259215	A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 Serrano, M, Hannon, GJ, Beach, D	Nature	1993
8741839	Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4 Guan, KL, Jenkins, CW, Li, Y, O'Keefe, CL, Noh, S, Wu, X, Zariwala, M, Matera, AG, Xiong, Y	Mol Biol Cell	1996
7859739	Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product Parry, D, Bates, S, Mann, DJ, Peters, G	EMBO J.	1995
8078588	p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest Hannon, GJ, Beach, D	Nature	1994
8001816	Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function Guan, KL, Jenkins, CW, Li, Y, Nichols, MA, Wu, X, O'Keefe, CL, Matera, AG, Xiong, Y	Genes Dev	1994