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Molecular and Cellular Biology
Article . 2016 . Peer-reviewed
License: ASM Journals Non-Commercial TDM
Data sources: Crossref
Molecular and Cellular Biology
Article . 2016
Data sources: u:cris
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The Late S-Phase Transcription Factor Hcm1 Is Regulated through Phosphorylation by the Cell Wall Integrity Checkpoint

Authors: Negishi, Takahiro; Veis, Jiri; Hollenstein, David; Sekiya, Mizuho; Ammerer, Gustav; Ohya, Yoshikazu;

The Late S-Phase Transcription Factor Hcm1 Is Regulated through Phosphorylation by the Cell Wall Integrity Checkpoint

Abstract

The cell wall integrity (CWI) checkpoint in the budding yeast Saccharomyces cerevisiae coordinates cell wall construction and cell cycle progression. In this study, we showed that the regulation of Hcm1, a late-S-phase transcription factor, arrests the cell cycle via the cell wall integrity checkpoint. Although the HCM1 mRNA level remained unaffected when the cell wall integrity checkpoint was induced, the protein level decreased. The overproduction of Hcm1 resulted in the failure of the cell wall integrity checkpoint. We identified 39 Hcm1 phosphorylation sites, including 26 novel sites, by tandem mass spectrometry analysis. A mutational analysis revealed that phosphorylation of Hcm1 at S61, S65, and S66 is required for the proper onset of the cell wall integrity checkpoint by regulating the timely decrease in its protein level. Hyperactivation of the CWI mitogen-activated protein kinase (MAPK) signaling pathway significantly reduced the Hcm1 protein level, and the deletion of CWI MAPK Slt2 resulted in a failure to decrease Hcm1 protein levels in response to stress, suggesting that phosphorylation is regulated by CWI MAPK. In conclusion, we suggest that Hcm1 is regulated negatively by the cell wall integrity checkpoint through timely phosphorylation and degradation under stress to properly control budding yeast proliferation.

Country
Austria
Keywords

3-BETA-GLUCAN SYNTHASE, Saccharomyces cerevisiae Proteins, 106002 Biochemie, 1, Molecular Sequence Data, PROTEIN, Saccharomyces cerevisiae, CYCLE TRANSCRIPTION, SACCHAROMYCES-CEREVISIAE, ACTIVATION, Cell Wall, Gene Expression Regulation, Fungal, KINASE, YEAST, NETWORK, Amino Acid Sequence, Phosphorylation, GENE-EXPRESSION, 106002 Biochemistry, Forkhead Transcription Factors, HOST STRAINS, Up-Regulation, Mutation, Mitogen-Activated Protein Kinases, Sequence Alignment

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
12
Top 10%
Average
Top 10%
bronze