Reactome | Dephosphorylation of cytoplasmic Cyclin B1/B2:phospho-Cdc2 (Thr 14, Tyr 15) complexes by CDC25B

Dephosphorylation of cytoplasmic Cyclin B1/B2:phospho-Cdc2 (Thr 14, Tyr 15) complexes by CDC25B

Stable Identifier

R-HSA-170161

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Dephosphorylation of cytoplasmic Cyclin B1/B2:phospho-Cdc2 (Thr 14, Tyr 15) complexes by CDC25B

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Activation of the mitotic cyclinB:Cdc2 (CCNB:CDK1) complexes at mitosis requires the removal of the inhibitory phosphate groups on Cdc2 (CDK1). This dephosphorylation is achieved by the activity of the CDC25 family of phosphatases, which act on both CCNB1 and CCNB2-bound CDK1 (Galaktionov and Beach 1991, Goda et al. 2003, Timofeev et al. 2010). The CDC25 members, CDC25A, CDC25B, and CDC25C are kept inactive during interphase and are activated at the G2/M transition. CCNB:CDK1 complexes appear to participate in the full activation of CDC25 in a process that involves an amplification loop (see Wolfe and Gould, 2004). The initial activation of the CCNB:CDK1 (cyclin B1:Cdc2 and cyclin-B2:Cdc2) complexes occurs in the cytoplasm in prophase (Jackman et al., 2003). CDC25B, which is present at highest concentrations in the cytoplasm at this time, is thought to trigger the activation of CCNB1:CDK1 (Lindqvist et al. 2004; Honda et al., 1993). Active CCNB1:CDK1 then phosphorylates CDC25C (contributing to its PLK1-mediated activation) and stabilizes CDC25A (Strausfeld et al., 1994; Hoffman et al.,1993; Mailand et al, 2002). This creates positive feedback loops that allows CDC25A and CDC25C to dephosphorylate and further activate CDK1. As active CDC25C is nuclear, it presumably predominantly contributes to activation of nuclear CDK1 (Strausfeld et al. 1994, Toyoshima-Morimoto et al. 2002, Bonnet, Coopman et al. 2008, Bonnet Mayonove et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
8440392	Dephosphorylation of human p34cdc2 kinase on both Thr-14 and Tyr-15 by human cdc25B phosphatase Honda, R, Ohba, Y, Nagata, A, Okayama, H, Yasuda, H	FEBS Lett	1993
1836978	Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins Galaktionov, K, Beach, D	Cell	1991
20360007	Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition Timofeev, O, Cizmecioglu, O, Settele, F, Kempf, T, Hoffmann, I	J. Biol. Chem.	2010
12411508	Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability Mailand, N, Podtelejnikov, AV, Groth, A, Mann, M, Lukas, J	EMBO J	2002
8119945	Activation of p34cdc2 protein kinase by microinjection of human cdc25C into mammalian cells. Requirement for prior phosphorylation of cdc25C by p34cdc2 on sites phosphorylated at mitosis. Strausfeld, U, Fernandez, A, Capony, JP, Girard, F, Lautredou, N, Derancourt, J, Labbe, JC, Lamb, NJ	J Biol Chem	1994
10827953	Rapid destruction of human Cdc25A in response to DNA damage. Mailand, N, Lukas, C, Syljuâsen, RG, Welcker, M, Lukas, J	Science	2000
12754270	The RRASK motif in Xenopus cyclin B2 is required for the substrate recognition of Cdc25C by the cyclin B-Cdc2 complex Goda, T, Ishii, T, Nakajo, N, Sagata, N, Kobayashi, H	J. Biol. Chem.	2003