Promotion of importin alpha-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3
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Promotion of importin alpha-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3. / Faul, Christian; Hüttelmaier, Stefan; Oh, Jun; Hachet, Virginie; Singer, Robert H; Mundel, Peter.
in: J CELL BIOL, Jahrgang 169, Nr. 3, 09.05.2005, S. 415-24.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Promotion of importin alpha-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3
AU - Faul, Christian
AU - Hüttelmaier, Stefan
AU - Oh, Jun
AU - Hachet, Virginie
AU - Singer, Robert H
AU - Mundel, Peter
PY - 2005/5/9
Y1 - 2005/5/9
N2 - 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 alpha 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.
AB - 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 alpha 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.
KW - 14-3-3 Proteins/metabolism
KW - Active Transport, Cell Nucleus/physiology
KW - Amino Acid Substitution/physiology
KW - Animals
KW - Cell Line
KW - Cell Nucleus/metabolism
KW - Humans
KW - Mice
KW - Microfilament Proteins/metabolism
KW - Models, Biological
KW - Mutation/physiology
KW - Myoblasts/metabolism
KW - Phosphorylation
KW - Protein Binding/physiology
KW - Protein Structure, Tertiary/physiology
KW - Protein Transport/physiology
KW - alpha Karyopherins/metabolism
U2 - 10.1083/jcb.200411169
DO - 10.1083/jcb.200411169
M3 - SCORING: Journal article
C2 - 15883195
VL - 169
SP - 415
EP - 424
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 3
ER -
