Reactome | Cyclin E:CDK2-mediated phosphorylation of RB1

Cyclin E:CDK2-mediated phosphorylation of RB1

Stable Identifier

R-HSA-188390

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle, Mitotic (Homo sapiens)
  - Mitotic G1 phase and G1/S transition (Homo sapiens)
    - G1/S Transition (Homo sapiens)
      - Cyclin E associated events during G1/S transition (Homo sapiens)
        
        Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes (Homo sapiens)
        
        Cyclin E:CDK2-mediated phosphorylation of RB1 (Homo sapiens)

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Cyclin E:CDK2-mediated phosphorylation of RB1

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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 Ezhevsky, SA, Ho, A, Becker-Hapak, M, Davis, PK, Dowdy, SF	Mol. Cell. Biol.	2001
11032757	Downregulation of cyclin D1 alters cdk 4- and cdk 2-specific phosphorylation of retinoblastoma protein Yu, B, Lane, ME, Pestell, RG, Albanese, C, Wadler, S	Mol. Cell Biol. Res. Commun.	2000
9891042	Retinoblastoma protein contains a C-terminal motif that targets it for phosphorylation by cyclin-cdk complexes Adams, PD, Li, X, Sellers, WR, Baker, KB, Leng, X, Harper, JW, Taya, Y, Kaelin WG, Jr	Mol Cell Biol	1999
24876129	Cyclin D activates the Rb tumor suppressor by mono-phosphorylation Narasimha, AM, Kaulich, M, Shapiro, GS, Choi, YJ, Sicinski, P, Dowdy, SF	Elife	2014
9190208	Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation Connell-Crowley, L, Harper, JW, Goodrich, DW	Mol Biol Cell	1997
9482921	Identification of a substrate-targeting domain in cyclin E necessary for phosphorylation of the retinoblastoma protein Kelly, BL, Wolfe, KG, Roberts, JM	Proc Natl Acad Sci U S A	1998
10207050	Cumulative effect of phosphorylation of pRB on regulation of E2F activity Brown, VD, Phillips, RA, Gallie, BL	Mol. Cell. Biol.	1999
9447971	Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes Lundberg, AS, Weinberg, RA	Mol. Cell. Biol.	1998
10499802	Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1 Harbour, JW, Luo, RX, Dei Santi, A, Postigo, AA, Dean, DC	Cell	1999