Reactome | Cyclin A/B1/B2 associated events during G2/M transition

Cyclin A/B1/B2 associated events during G2/M transition

Stable Identifier

R-HSA-69273

DOI

10.3180/R-HSA-69273.9

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Cyclin A/B1/B2 associated events during G2/M transition

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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).

Literature References

PubMed ID	Title	Journal	Year
35402801	Cell cycle regulation and hematologic malignancies Kumar, SK, Dai, Y, Wu, W, Jin, F	Blood Sci	2019
10354564	All aboard the cyclin train: subcellular trafficking of cyclins and their CDK partners Yang, J, Kornbluth, S	Trends Cell Biol	1999
17533373	Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2 Sobczak-Thépot, J, de Gramont, A, Bellanger, S	Oncogene	2007
11238451	The localization of human cyclins B1 and B2 determines CDK1 substrate specificity and neither enzyme requires MEK to disassemble the Golgi apparatus Orrechia, S, Draviam, VM, Pines, J, Pardi, R, Lowe, M	J Cell Biol	2001
7737117	Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus Firth, M, Jackman, M, Pines, J	EMBO J	1995
31078132	Functions of cyclins and CDKs in mammalian gametogenesis† Wang, PJ, Wolgemuth, DJ, Chotiner, JY	Biol Reprod	2019
33030403	Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies Liu, SY, Ikegami, K	Nucleus	2020
15876871	CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control and a target for drugs? Johnson, LN, Lolli, G	Cell Cycle	2005
18228324	Overview of protein phosphorylation Sefton, BM	Curr Protoc Cell Biol	2001
31469407	Orchestration of the spindle assembly checkpoint by CDK1-cyclin B1 Alfonso-Pérez, T, Gruneberg, U, Hayward, D	FEBS Lett	2019
36105360	Structural, enzymatic and spatiotemporal regulation of PP2A-B55 phosphatase in the control of mitosis Lacroix, B, Lorca, T, Castro, A	Front Cell Dev Biol	2022
30736436	Phosphatases in Mitosis: Roles and Regulation Moura, M, Conde, C	Biomolecules	2019
10395539	Translocation of cyclin B1 to the nucleus at prophase requires a phosphorylation-dependent nuclear import signal Pines, J, Hagting, A, Simpson, K, Jackman, M	Curr Biol	1999
31712253	DNA replication and mitotic entry: A brake model for cell cycle progression Lindqvist, A, Lemmens, B	J Cell Biol	2019