Meta-Biol

• Pathways

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).