Cell cycle-dependent phosphorylation and regulation of cellular differentiation

Author:

Hardwick Laura J.A.12,Azzarelli Roberta134,Philpott Anna13

Affiliation:

1. Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge Biomedical Campus, Cambridge CB2 0XZ, U.K.

2. Peterhouse, Cambridge CB2 1RD, U.K.

3. Wellcome Trust/MRC Centre for Stem Cell Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, U.K.

4. Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, U.K.

Abstract

Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation. Here, we focus on a direct mechanistic link involving phosphorylation of differentiation-associated transcription factors by cell cycle-associated Cyclin-dependent kinases. We discuss examples from the three embryonic germ layers to illustrate this regulatory mechanism that co-ordinates the balance between cell proliferation and differentiation.

Publisher

Portland Press Ltd.

Subject

Biochemistry

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