14-3-3 proteins are phosphoserine/threonine-binding proteins that play important roles in many regulatory processes, including intracellular protein targeting. 14-3-3 proteins can anchor target proteins in the cytoplasm and in the nucleus or can mediate their nuclear export. So far, no role for 14-3-3 in mediating nuclear import has been described. There is also mounting evidence that nuclear import is regulated by the phosphorylation of cargo proteins, but the underlying mechanism remains elusive. Myopodin is a dual-compartment, actin-bundling protein that functions as a tumor suppressor in human bladder cancer. In muscle cells, myopodin redistributes between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion. We show that importin α binding and the subsequent nuclear import of myopodin are regulated by the serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3. These results establish a novel paradigm for the promotion of nuclear import by 14-3-3 binding. They provide a molecular explanation for the phosphorylation-dependent nuclear import of nuclear localization signal-containing cargo proteins.
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9 May 2005
Article|
May 09 2005
Promotion of importin α–mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3
Christian Faul,
Christian Faul
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
4Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
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Stefan Hüttelmaier,
Stefan Hüttelmaier
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
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Jun Oh,
Jun Oh
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
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Virginie Hachet,
Virginie Hachet
3European Molecular Biology Laboratory, 69117 Heidelberg, Germany
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Robert H. Singer,
Robert H. Singer
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
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Peter Mundel
Peter Mundel
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
4Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
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Christian Faul
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
4Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
Stefan Hüttelmaier
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
Jun Oh
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
Virginie Hachet
3European Molecular Biology Laboratory, 69117 Heidelberg, Germany
Robert H. Singer
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
Peter Mundel
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
4Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029
Correspondence to Peter Mundel: [email protected]
Abbreviations used in this paper: λ-PPase, λ protein phosphatase; IP, immunoprecipitation; LMB, leptomycin B; NLS, nuclear localization signal; pGEX, glutathione S-transferase fusion vector.
Received:
November 29 2004
Accepted:
March 10 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (3): 415–424.
Article history
Received:
November 29 2004
Accepted:
March 10 2005
Citation
Christian Faul, Stefan Hüttelmaier, Jun Oh, Virginie Hachet, Robert H. Singer, Peter Mundel; Promotion of importin α–mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3 . J Cell Biol 9 May 2005; 169 (3): 415–424. doi: https://doi.org/10.1083/jcb.200411169
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