Caffeine as a tool for investigating the integration of Cdc25 phosphorylation, activity and ubiquitin-dependent degradation in Schizosaccharomyces pombe

Article


Alao, J. and Sunnerhagen, P. 2020. Caffeine as a tool for investigating the integration of Cdc25 phosphorylation, activity and ubiquitin-dependent degradation in Schizosaccharomyces pombe. Cell Division. 15 (10).
AuthorsAlao, J. and Sunnerhagen, P.
Abstract

The evolutionarily conserved Cdc25 phosphatase is an essential protein that removes inhibitory phosphorylation moieties on the mitotic regulator Cdc2. Together with the Wee1 kinase, a negative regulator of Cdc2 activity, Cdc25 is thus a central regulator of cell cycle progression in Schizosaccharomyces pombe. The expression and activity of Cdc25 is dependent on the activity of the Target of Rapamycin Complex 1 (TORC1). TORC1 inhibition leads to the activation of Cdc25 and repression of Wee1, leading to advanced entry into mitosis. Withdrawal of nitrogen leads to rapid Cdc25 degradation via the ubiquitin- dependent degradation pathway by the Pub1 E3- ligase. Caffeine is believed to mediate the override of DNA damage checkpoint signalling, by inhibiting the activity of the ataxia telangiectasia mutated (ATM)/Rad3 homologues. This model remains controversial, as TORC1 appears to be the preferred target of caffeine in vivo. Recent studies suggest that caffeine induces DNA damage checkpoint override by inducing the nuclear accumulation of Cdc25 in S. pombe. Caffeine may thus modulate Cdc25 activity and stability via inhibition of TORC1. A clearer understanding of the mechanisms by which caffeine stabilises Cdc25, may provide novel insights into how TORC1 and DNA damage signalling is integrated.

JournalCell Division
Journal citation15 (10)
ISSN1747-1028
Year2020
PublisherBioMed Central
Publisher's version
License
File Access Level
Anyone
Digital Object Identifier (DOI)doi:10.1186/s13008-020-00066-1
Web address (URL)https://doi.org/10.1186/s13008-020-00066-1
Publication dates
Online29 Jun 2020
Publication process dates
Deposited06 Jul 2020
Accepted08 Jun 2020
FunderSwedish Cancer Fund
Carl Tryggers foundation
Copyright holder© 2020 The Authors
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