PreprintCited by 115Signaling Pathways in DiseaseFungal and yeast genetics researchNuclear Structure and Function

Calcineurin-dependent regulation of Crz1p nuclear export requires Msn5p and a conserved calcineurin docking site

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Boustany, Leila M., Cyert, Martha S.·2002·Genes & Development

Abstract

Calcineurin, a conserved Ca 2+/calmodulin-regulated protein phosphatase, plays a crucial role in Ca 2+ signaling in a wide variety of cell types. In Saccharomyces cerevisiae, calcineurin positively regulates transcription in response to stress by dephosphorylating the transcription factor Crz1p/Tcn1p. Dephosphorylation promotes Crz1p nuclear localization in part by increasing the efficiency of its nuclear import. In this work, we show that calcineurin-dependent dephosphorylation of Crz1p also down-regulates its nuclear export. Using a genetic approach, we identify Msn5p as the exportin for Crz1p. In addition, we define the Crz1p nuclear export signal (NES) and show that it interacts with Msn5p in a phosphorylation-dependent manner. This indicates that calcineurin regulates Crz1p nuclear export by dephosphorylating and inactivating its NES. Finally, we define a motif in Crz1p, PIISIQ, similar to the PxIxIT docking site for calcineurin on the mammalian transcription factor NFAT, that mediates the in vivo interaction between calcineurin and Crz1p and is required for calcineurin-dependent regulation of Crz1p nuclear export and activity. Therefore, in yeast as in mammals, a docking site is required to target calcineurin to its substrate such that it can dephosphorylate it efficiently.

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  1. Ausubel, F.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., and Struhl, K. 1987. Current protocols in molecular biology. John Wiley, New York, NY.
  2. Stathopoulos, A.M. 1998. "Calcineurin regulates the CRZ1 transcription factor to control gene expression in Saccharo- myces cerevisiae." Ph.D. thesis, Stanford University, Stan- ford, CA.

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Authors
Boustany, L. M., & Cyert, M. S.
Affiliations
Stanford University (US)
Venue
Genes & Development
Published
2002-03-01
Volume
16
Issue
5
Pages
608-619
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2110510554
Cited by
115
References
62
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 6
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (5 T32 GM07276, GM-48729, T32GM007276, R01GM048729)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
calcineurin, nuclear export, nuclear export signal, protein dephosphorylation, NFAT, transcription factor regulation, Ca2+/calmodulin signaling, Saccharomyces cerevisiae, exportins
MeSH terms
Binding Sites, Carrier Proteins, Cell Nucleus, DNA-Binding Proteins, Mutation, Protein Binding, Saccharomyces cerevisiae, Transcription Factors, Trans-Activators, Conserved Sequence, Sequence Deletion, Calcineurin, Amino Acid Motifs, Protein Sorting Signals, Active Transport, Cell Nucleus, Karyopherins, Saccharomyces cerevisiae Proteins

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