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Curr Genet. 2016 May;62(2):271-6. doi: 10.1007/s00294-015-0535-5. Epub 2015 Nov 21.

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

Author information

1
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA. jennifer.benanti@umassmed.edu.

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:

Calcineurin; Cell cycle; Cyclin-dependent kinase; Gene expression; Hcm1

PMID:
26590602
DOI:
10.1007/s00294-015-0535-5
[Indexed for MEDLINE]

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