Control of cell cycle progression by phosphorylation of cyclin-dependent kinase (CDK) substrates

Cell Cycle and Cancer Unit, St Vincent's Institute of Medical Research, The University of Melbourne, Fitzroy, Melbourne, Victoria 3065, Australia.
Bioscience Reports (Impact Factor: 2.64). 03/2010; 30(4):243-55. DOI: 10.1042/BSR20090171
Source: PubMed


The eukaryotic cell cycle is a fundamental evolutionarily conserved process that regulates cell division from simple unicellular organisms, such as yeast, through to higher multicellular organisms, such as humans. The cell cycle comprises several phases, including the S-phase (DNA synthesis phase) and M-phase (mitotic phase). During S-phase, the genetic material is replicated, and is then segregated into two identical daughter cells following mitotic M-phase and cytokinesis. The S- and M-phases are separated by two gap phases (G1 and G2) that govern the readiness of cells to enter S- or M-phase. Genetic and biochemical studies demonstrate that cell division in eukaryotes is mediated by CDKs (cyclin-dependent kinases). Active CDKs comprise a protein kinase subunit whose catalytic activity is dependent on association with a regulatory cyclin subunit. Cell-cycle-stage-dependent accumulation and proteolytic degradation of different cyclin subunits regulates their association with CDKs to control different stages of cell division. CDKs promote cell cycle progression by phosphorylating critical downstream substrates to alter their activity. Here, we will review some of the well-characterized CDK substrates to provide mechanistic insights into how these kinases control different stages of cell division.

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Available from: Randy Suryadinata, Jul 15, 2014
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    • "Rather, within the group of genes regulated in dwarfy leaves, we observed the repression of a large class of cell cycle genes including CYCLIN-DEPENDENT KINASE1 (CDK1), CYCLIN A, and CYCLIN B1 (Table 2). In eukaryotic cells, CYCLIN A initiates the cellular transition from G2 to prophase after which CYCLIN B1 enters the nucleus and, together with CDK1, induces mitosis by phosphorylation and activation of enzymes regulating chromatin condensation, nuclear membrane breakdown and mitosis-specific microtubule and microfilament re-orientation (Nigg, 2001;Smits and Medema, 2001;Gavet and Pines, 2010;Suryadinata et al., 2010;Rattani et al., 2014). As this whole suite of proteins is necessary for cellular division, repression of their transcription in the leaves of dwarfy, as compared to wild-type leaves, is likely the key pathway by which leaf size is being affected. "
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    • "In early G1 phase, Cyclin D binds to Cdk4 and/or Cdk6 to form cyclin-Cdk complexes, resulting in the activation of Cdks. Phosphorylation of Rb protein by the Cyclin D-Cdk4/6 complex in turn allows the expression of other cell cycle genes, such as Cyclin E. Association between Cyclin E and Cdk2 then leads to the phosphorylation and degradation of p27, allowing the transition from G1 to S phase [26], [27], [43]. The regulation of cyclins and Cdks expression by OEOA, together with the ability of OEOA to suppress RAMP expression, strongly suggest that OEOA inhibits proliferation of leukemia cells by modulating cell cycle protein expression. "
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    • "The cell cycle in eukaryotic organisms is a very well-regulated process, divided in four phases: G1 (cell enlargement), S (DNA replication), G2 and M (cytokinesis) (Suryadinata et al., 2010). In general, cells from differentiated animal tissues, such as hepatocytes, are arrested in the G1 – S transition (Nelsen et al., 2003). "
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