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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    • "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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    • "The key cell cycle drivers are the Cyclin-dependent kinases (CDK), a family of serine/threonine kinases. Different CDKs play a role at different steps of the cell cycle: CDK2, 4, and 6 are active during G1, CDK2 during G1 and S phase and CDK1 during G2 and mitosis [8,9,10]. CDK activity is controlled by several mechanisms, which include the accumulation of the activating subunit Cyclin, the subcellular localization, CDK phosphorylation status, and CDK inhibitors (CKI). "
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