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PMID: 14597664 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein kinase I.

Genes & development ·Vol. 17 ·No. 21 ·2003-11-01 ·Pages 2698-708

Kafadar KA, Zhu H, Snyder M, Cyert MS

Abstract

Calcineurin is a Ca2+/calmodulin-regulated protein phosphatase required for Saccharomyces cerevisiae to respond to a variety of environmental stresses. Calcineurin promotes cell survival during stress by dephosphorylating and activating the Zn-finger transcription factor Crz1p/Tcn1p. Using a high-throughput assay, we screened 119 yeast kinases for their ability to phosphorylate Crz1p in vitro and identified the casein kinase I homolog Hrr25p. Here we show that Hrr25p negatively regulates Crz1p activity and nuclear localization in vivo. Hrr25p binds to and phosphorylates Crz1p in vitro and in vivo. Overexpression of Hrr25p decreases Crz1p-dependent transcription and antagonizes its Ca2+-induced nuclear accumulation. In the absence of Hrr25p, activation of Crz1p by Ca2+/calcineurin is potentiated. These findings represent the first identification of a negative regulator for Crz1p, and establish a novel physiological role for Hrr25p in antagonizing calcineurin signaling.

MeSH Terms
Calcineurin/metabolism Casein Kinase I Casein Kinases DNA-Binding Proteins Gene Expression Regulation, Fungal/physiology Protein Kinases/genetics,metabolism Protein Transport Saccharomyces cerevisiae Proteins/genetics,metabolism Signal Transduction/physiology Trans-Activators/metabolism Transcription Factors
Chemicals
CRZ1 protein, S cerevisiae DNA-Binding Proteins Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Protein Kinases Casein Kinase I Casein Kinases HRR25 protein, S cerevisiae Calcineurin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kafadar Kimberly A
Department of Biological Sciences Stanford University, Stanford, California, 94305-5020, USA.
Zhu Heng
Snyder Michael
Cyert Martha S
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1140603
Published
2003-11-01
Pages
2698-708
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC280619
Subset
IM
Grants
NIGMS NIH HHS · R01 GM048729 · United States
NIGMS NIH HHS · GM62480-03 · United States
NIGMS NIH HHS · T32 GM007276 · United States
NIGMS NIH HHS · GM-48729 · United States
NIGMS NIH HHS · R01 GM062480 · United States
NIGMS NIH HHS · 5T32GM07276 · United States
External Links
PubMed source DOI: 10.1101/gad.1140603 PMC Full Text View journal details
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