Cyclin E:CDK2-mediated phosphorylation of RB1

Stable Identifier
Reaction [transition]
Homo sapiens
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Cyclin E (CCNE1 or CCNE2) forms a complex with CDK2 and collaborates with the cyclin D-dependent kinases CDK4 and CDK6 in phosphorylating RB1 (Kelly et al.1998, Adams et al.1999). CDK4/CDK6-mediated monophosphorylation of RB1 is a pre-requisite for hyperphosphorylation and full inactivation of RB1 mediated by the CCNE:CDK2 complex (Connell-Crowley et al. 1997, Lundberg and Weinberg 1998, Brown et al. 1999, Harbour et al. 1999, Yu et al. 2000, Ezhevsky et al. 2001), with monophosphorylated RB1 being phosphorylated on 14 CDK sites out of 16 predicted sites (Narasimha et al. 2014).

Literature References
PubMed ID Title Journal Year
11416152 Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo

Becker-Hapak, M, Davis, PK, Ezhevsky, SA, Ho, A, Dowdy, SF

Mol. Cell. Biol. 2001
11032757 Downregulation of cyclin D1 alters cdk 4- and cdk 2-specific phosphorylation of retinoblastoma protein

Wadler, S, Albanese, C, Pestell, RG, Lane, ME, Yu, B

Mol. Cell Biol. Res. Commun. 2000
9891042 Retinoblastoma protein contains a C-terminal motif that targets it for phosphorylation by cyclin-cdk complexes

Li, X, Taya, Y, Leng, X, Kaelin WG, Jr, Sellers, WR, Adams, PD, Baker, KB, Harper, JW

Mol Cell Biol 1999
24876129 Cyclin D activates the Rb tumor suppressor by mono-phosphorylation

Choi, YJ, Kaulich, M, Sicinski, P, Shapiro, GS, Dowdy, SF, Narasimha, AM

Elife 2014
9190208 Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation

Connell-Crowley, L, Goodrich, DW, Harper, JW

Mol Biol Cell 1997
9482921 Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein

Wolfe, KG, Kelly, BL, Roberts, JM

Proc Natl Acad Sci U S A 1998
10207050 Cumulative effect of phosphorylation of pRB on regulation of E2F activity

Gallie, BL, Brown, VD, Phillips, RA

Mol. Cell. Biol. 1999
9447971 Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes

Weinberg, RA, Lundberg, AS

Mol. Cell. Biol. 1998
10499802 Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1

Dean, DC, Dei Santi, A, Postigo, AA, Harbour, JW, Luo, RX

Cell 1999
Catalyst Activity

cyclin-dependent protein serine/threonine kinase activity of CCNE:p-T160-CDK2:hypophosphorylated RB1 [nucleoplasm]

Orthologous Events
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