Cited by 63Nuclear Structure and FunctionFungal and yeast genetics researchSignaling Pathways in Disease

Calcineurin-dependent nuclear import of the transcription factor Crz1p requires Nmd5p

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Polizotto, Renée S., Cyert, Martha S.·2001·The Journal of Cell Biology

Abstract

Calcineurin is a conserved Ca2+/calmodulin-specific serine-threonine protein phosphatase that mediates many Ca2+-dependent signaling events. In yeast, calcineurin dephosphorylates Crz1p, a transcription factor that binds to the calcineurin-dependent response element, a 24-bp promoter element. Calcineurin-dependent dephosphorylation of Crz1p alters Crz1p nuclear localization. This study examines the mechanism by which calcineurin regulates the nuclear localization of Crz1p in more detail. We describe the identification and characterization of a novel nuclear localization sequence (NLS) in Crz1p, which requires both basic and hydrophobic residues for activity, and show that the karyopherin Nmd5p is required for Crz1p nuclear import. We also demonstrate that the binding of Crz1p to Nmd5p is dependent upon its phosphorylation state, indicating that nuclear import of Crz1p is regulated by calcineurin. Finally, we demonstrate that residues in both the NH2- and COOH-terminal portions of Crz1p are required for regulated Crz1p binding to Nmd5p, supporting a model of NLS masking for regulating Crz1p nuclear import.

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  1. Ausubel, F.M., R. Brent, R.E. Kingston, D.D. Moore, J.G. Seidman, J.A. Smith, and K. Struhl. 1994. Current protocols in molecular biology. Vols. 1 and 2. John Wiley & Sons Inc., New York.

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Authors
Polizotto, R. S., & Cyert, M. S.
Affiliations
  • Department of Biological Sciences, Stanford University, Stanford, CA 94305
  • Stanford University (US)
Venue
The Journal of Cell Biology
Published
2001-09-03
Volume
154
Issue
5
Pages
951-960
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W1991532862
Cited by
63
References
46
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2022: 5 · 2021: 2 · 2019: 1 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 5
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM-48728)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
calcineurin, nuclear import, nuclear localization signal, karyopherins, Ca2+/calmodulin signaling, Saccharomyces cerevisiae
MeSH terms
Amino Acid Sequence, Cell Nucleus, DNA-Binding Proteins, Fungal Proteins, Guanosine Triphosphate, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Recombinant Fusion Proteins, Transcription Factors, Yeasts, Immunoblotting, Trans-Activators, Zinc Fingers, Protein Structure, Tertiary, Genes, Reporter, Calcineurin, Nuclear Localization Signals, Monomeric GTP-Binding Proteins, Protein Sorting Signals, Active Transport, Cell Nucleus, Saccharomyces cerevisiae Proteins

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