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Current Genetics

, Volume 62, Issue 2, pp 271–276 | Cite as

Create, activate, destroy, repeat: Cdk1 controls proliferation by limiting transcription factor activity

  • Jennifer A. BenantiEmail author
Review

Abstract

Progression through the cell cycle is controlled by a network of transcription factors that coordinate gene expression with cell-cycle events. One transcriptional activator in this network in budding yeast is the forkhead protein Hcm1, which controls the expression of genes that are transcribed during S-phase. Hcm1 activity is coordinated with the cell cycle via its regulation by cyclin-dependent kinase (Cdk1), which both activates Hcm1 and targets it for degradation, through phosphorylation of distinct sites. The mechanisms controlling the differential phosphorylation timing of the activating and destabilizing phosphosites are not clear. However, a recent study shows that the phosphatase calcineurin specifically removes activating phosphates from Hcm1 when cells are exposed to environmental stress, thus extinguishing its activity and slowing proliferation under unfavorable growth conditions. This regulatory mechanism, whereby a phosphatase actively alters the distribution of phosphosites on a cell cycle-regulatory transcription factor to elicit a change in cellular proliferation, adds an additional layer of complexity to the regulatory network controlling the cell cycle. Furthermore, this regulatory paradigm is likely to be a conserved mode of phosphoregulation that controls the cell cycle in diverse systems.

Keywords

Cell cycle Gene expression Cyclin-dependent kinase Hcm1 Calcineurin 

Notes

Acknowledgments

I thank Tom Fazzio and members of the Benanti laboratory for comments on the manuscript. This work was supported by a Grant from the Richard and Susan Smith Family Foundation.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Molecular, Cell and Cancer BiologyUniversity of Massachusetts Medical SchoolWorcesterUSA

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