Promotion of importin α-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3

Christian H Faul, Stefan Hüttelmaier, Jun Oh, Virginie Hachet, Robert H. Singer, Peter Mundel

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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 a 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.

Original languageEnglish
Pages (from-to)415-424
Number of pages10
JournalJournal of Cell Biology
Volume169
Issue number3
DOIs
StatePublished - May 9 2005
Externally publishedYes

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Karyopherins
14-3-3 Proteins
Cell Nucleus Active Transport
Carrier Proteins
Phosphorylation
Threonine
Cytoplasm
Proteins
Phosphoserine
Nuclear Localization Signals
Protein Transport
Urinary Bladder Neoplasms
Muscle Cells
Serine
Actins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Promotion of importin α-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3. / Faul, Christian H; Hüttelmaier, Stefan; Oh, Jun; Hachet, Virginie; Singer, Robert H.; Mundel, Peter.

In: Journal of Cell Biology, Vol. 169, No. 3, 09.05.2005, p. 415-424.

Research output: Contribution to journalArticle

Faul, Christian H ; Hüttelmaier, Stefan ; Oh, Jun ; Hachet, Virginie ; Singer, Robert H. ; Mundel, Peter. / Promotion of importin α-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3. In: Journal of Cell Biology. 2005 ; Vol. 169, No. 3. pp. 415-424.
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