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Cell cycle progression is regulated by activation of cyclin-dependent protein kinases at G1/S, S/G2, and G2/M transitions (reviewed in Lemmens and Lindqvist 2019). Completion of DNA replication at the S/G2 transition allows activation of CDK1 and PLK1. Recent evidence implies that the activation of Cyclin A:CDK1 (CCNA:CDK1) complexes promotes the activation of AURKA, which promotes the activation of PLK1, which then promotes the activation of Cyclin B:CDK1 (CCNB:CDK1) complexes (reviewed in Pintard and Archambault 2018, Lemmens and Lindqvist 2019, Moura and Conde 2019). Inhibitory PKMYT1 and WEE1 kinases prevent premature activation of CDK1 complexes (reviewed in Lemmens and Lindqvist 2019). The CDC25 family phosphatases (CDC25A, CDC25B, and CDC25C), activated at G2/M transition, remove the inhibitory phosphorylations and, together with the activating phosphorylation mediated by the CAK complex (reviewed in Lolli and Johnson 2005), enable the full activation of CDK1 complexes (reviewed in Lemmens and Lindqvist 2019, Moura and Conde 2019). CCNA:CDK1 and CCNB:CDK1 complexes phosphorylate a large number of proteins involved in mitosis (M phase) (reviewed in Sefton 2001), including lamins (reviewed in Lemmens and Lindqvist 2019, Liu and Ikegami 2020) and other proteins involved in nuclear envelope breakdown (reviewed in Lindqvist et al. 2009, Lacroix et al. 2022), proteins involved in mitotic spindle formation (reviewed in Hayward et al. 2019, Lacroix et al. 2022), and proteins involved in disassembly of the Golgi apparatus (reviewed in Preisinger and Barr 2005). While CDK1 complexes may exhibit a high level of redundancy in vitro (Bellanger et al. 2007), their substrate specificity in vivo is partially determined by their subcellular localization, with CCNA:CDK1 complexes being mainly nuclear, the CCNB1:CDK1 complex being mainly cytosolic, and the CCNB2:CDK1 complex localizing mainly to the Golgi membrane (Jackman et al. 1995, Hagting et al. 1999, Dravian et al. 2001, reviewed in Yang and Kornbluth 1999). In addition, while CCNA2, CCNB1, and CCNB2 are ubiquitously expressed, CCNA1 is predominantly expressed in the testes and plays an important role in meiosis (reviewed in Chotiner et al. 2019), but it is also implicated in mitosis in specific cell types, such as hematopoietic stem cells (reviewed in Dai et al. 2019). CCNB3 functions exclusively in meiosis (reviewed in Chotiner et al. 2019).
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