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Cell cycle-dependent phosphorylation and regulation of cellular differentiation.

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Hardwick, Laura JA 
Azzarelli, Roberta 


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.



cell cycle, cell differentiation, phosphorylation/dephosphorylation, transcription factors, Animals, Cell Cycle, Cell Differentiation, Cell Lineage, Cell Proliferation, Chromatin, Cyclin-Dependent Kinases, Ectoderm, Embryonic Development, Epigenesis, Genetic, Homeostasis, Humans, Mesoderm, Phosphorylation, Proteome, Stem Cells, Transcription Factors, Transcriptome

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Biochem Soc Trans

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Portland Press Ltd.
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/K018329/1)
Medical Research Council (MR/L021129/1)
This work was funded by MRC Research Grants (MR/K018329/1 (AP/RA), MR/L021129/1 (AP)Neuroblastoma UK (AP) and the Rosetrees and Stoneygate Trusts (AP/RA). LH is supported by a Peterhouse Research Fellowship