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Cyclin-Dependent Kinase (CDK) Inhibitors pp 155–166Cite as

Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1336))

Abstract

Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

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Authors and Affiliations

  1. Department of Chemistry and Molecular Biology, University of Gothenburg, 462, 405 30, Gothenburg, Sweden

    Sanjiv Risal, Deepak Adhikari & Kui Liu

Authors
  1. Sanjiv Risal
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  2. Deepak Adhikari
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  3. Kui Liu
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Corresponding author

Correspondence to Sanjiv Risal .

Editor information

Editors and Affiliations

  1. Medicinal Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain

    Mar Orzáez

  2. Medicinal Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain

    Mónica Sancho Medina

  3. IBV-CSIC and Centro de Investigación Príncipe Felipe, Valencia, Spain

    Enrique Pérez-Payá

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Risal, S., Adhikari, D., Liu, K. (2016). Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs. In: Orzáez, M., Sancho Medina, M., Pérez-Payá, E. (eds) Cyclin-Dependent Kinase (CDK) Inhibitors. Methods in Molecular Biology, vol 1336. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2926-9_13

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  • DOI: https://doi.org/10.1007/978-1-4939-2926-9_13

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2925-2

  • Online ISBN: 978-1-4939-2926-9

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