Formation of CDK4/6:CCND complexes

Stable Identifier
Homo sapiens
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The cyclin dependent kinase CDK4 or CDK6 forms a complex with one of the cyclin D family (CCND) members: cyclin D1 (CCND1), cyclin D2 (CCND2) or cyclin D3 (CCND3) (Matsushime et al. 1992, Meyerson and Harlow 1994, La Baer et al. 1997, Bagui et al. 2003, Cerqueira et al. 2014). This association is regulated by mitogenic pathways (Cheng et al. 1998, Depoortere et al. 1998). While the binding of Cip/Kip CDK-inhibitors (CDKIs) (CDKNA1 - p21Cip, CDKN1B - p27Kip or CDKN1C - p57Kip2) stabilizes CDK4/6:CCND complexes by decreasing their dissociation rate (La Baer et al. 1997; reviewed by Sherr and Roberts 1999), CIP/KIP CDKIs are not needed for binding of CDK4 or CDK6 to CCNDs and activity of CDK4/6:CCND complexes (Bagui et al. 2000, Sugimoto et al. 2002, Bagui et al. 2003, Cerqueira et al. 2014; reviewed by Bockstaele et al 2006).

Literature References
PubMed ID Title Journal Year
1423597 Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins

Matsushime, H, Sherr, CJ, Ewen, ME, Hanks, SK, Strom, DK, Roussel, MF, Kato, JY

Cell 1992
12444543 Activation of cyclin D1-kinase in murine fibroblasts lacking both p21(Cip1) and p27(Kip1)

Wilks, DP, Tamai, K, Serrano, M, Hara, E, Sugimoto, M, Pantoja, C, Okumura, K, Huot, TJ, Martin, N

Oncogene 2002
9508775 A requirement for cyclin D3-cyclin-dependent kinase (cdk)-4 assembly in the cyclic adenosine monophosphate-dependent proliferation of thyrocytes

Depoortere, F, Dumont, JE, Van Keymeulen, A, Costagliola, S, Dremier, S, Roger, PP, Lukas, J, Bartkova, J, Bartek, J

J. Cell Biol. 1998
24515438 Genetic characterization of the role of the Cip/Kip family of proteins as cyclin-dependent kinase inhibitors and assembly factors

Barbacid, M, Symonds, CE, Santamaría, D, Cerqueira, A, Odajima, J, Martín, A, Dubus, P

Mol. Cell. Biol. 2014
14517297 P27Kip1 and p21Cip1 are not required for the formation of active D cyclin-cdk4 complexes

Pledger, WJ, Mohapatra, S, Bagui, TK, Haura, E

Mol. Cell. Biol. 2003
10385618 CDK inhibitors: positive and negative regulators of G1-phase progression

Roberts, JM, Sherr, CJ

Genes Dev. 1999
17092340 Regulation of CDK4

Paternot, S, Kooken, H, Coulonval, K, Bockstaele, L, Roger, PP

Cell Div 2006
11073976 Analysis of cyclin D3-cdk4 complexes in fibroblasts expressing and lacking p27(kip1) and p21(cip1)

Agrawal, D, Jackson, RJ, Pledger, WJ, Bagui, TK

Mol. Cell. Biol. 2000
9106657 New functional activities for the p21 family of CDK inhibitors.

LaBaer, J, Garrett, MD, Fattaey, A, Harlow, E, Sandhu, C, Chou, HS, Stevenson, LF, Slingerland, JM

Genes Dev 1997
9448290 Assembly of cyclin D-dependent kinase and titration of p27Kip1 regulated by mitogen-activated protein kinase kinase (MEK1)

Sexl, V, Sherr, CJ, Cheng, M, Roussel, MF

Proc. Natl. Acad. Sci. U.S.A. 1998
8114739 Identification of G1 kinase activity for cdk6, a novel cyclin D partner

Meyerson, M, Harlow, E

Mol. Cell. Biol. 1994
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