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

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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

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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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Authors: Boustany, L. M., & Cyert, M. S.
Affiliations: Stanford University (US)
ORCID: Boustany, Leila M.
Cyert, Martha S.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2002-03-01
Volume: 16
Issue: 5
Pages: 608-619
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.967602
PMC: PMC155349
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: bronze
doi.org
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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Calcineurin-dependent regulation of Crz1p nuclear export requires Msn5p and a conserved calcineurin docking site

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