Reactome | Cip/Kip CDK inhibitors bind CDK4/6:CCND complexes

Cip/Kip CDK inhibitors bind CDK4/6:CCND complexes

Stable Identifier

R-HSA-8941915

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Cip/Kip CDK inhibitors bind CDK4/6:CCND complexes

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Binding of CDK inhibitors of the Cip/Kip family, CDKNA1 (p21Cip), CDKN1B (p27Kip) or CDKN1C (p57Kip2) to the complex of CDK4 or CDK6 and cyclin D family members (CCND1, CCND2 or CCND3), inhibits kinase activity of the CDK4/6:CCND complexes but at the same time increases their stability and, hence, their abundance (La Baer et al. 1997, Bagui et al. 2003, Cerqueira et al. 2014; reviewed by Bockstaele et al. 2006). Based on structural studies of CDKN1B, Cip/Kip inhibitors simultaneously interact with CDK4/6 and CCNDs (Liu et al. 2010). Phosphorylation of CDKN1B on threonine residues T157 and T198 by activated AKT in early G1 may precede binding of CDKN1B to CDK4/6:CCND complexes (Larrea et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
20843055	Structural and functional analysis of cyclin D1 reveals p27 and substrate inhibitor binding requirements Liu, S, Bolger, JK, Kirkland, LO, Premnath, PN, McInnes, C	ACS Chem. Biol.	2010
24515438	Genetic characterization of the role of the Cip/Kip family of proteins as cyclin-dependent kinase inhibitors and assembly factors Cerqueira, A, Martín, A, Symonds, CE, Odajima, J, Dubus, P, Barbacid, M, Santamaría, D	Mol. Cell. Biol.	2014
14517297	P27Kip1 and p21Cip1 are not required for the formation of active D cyclin-cdk4 complexes Bagui, TK, Mohapatra, S, Haura, E, Pledger, WJ	Mol. Cell. Biol.	2003
18710949	Phosphorylation of p27Kip1 regulates assembly and activation of cyclin D1-Cdk4 Larrea, MD, Liang, J, Da Silva, T, Hong, F, Shao, SH, Han, K, Dumont, D, Slingerland, JM	Mol. Cell. Biol.	2008
17092340	Regulation of CDK4 Bockstaele, L, Coulonval, K, Kooken, H, Paternot, S, Roger, PP	Cell Div	2006
9106657	New functional activities for the p21 family of CDK inhibitors. LaBaer, J, Garrett, MD, Stevenson, LF, Slingerland, JM, Sandhu, C, Chou, HS, Fattaey, A, Harlow, E	Genes Dev	1997