1. Promotion of importin α -- mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3.
- Author
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Fciul, Christian, Hütlelmaier, Stefan, Oh, Jun, Hachet, Virginie, Singer, Robert H., and Mundel, Peter
- Subjects
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CARRIER proteins , *PROTEIN binding , *BLADDER cancer , *PHOSPHORYLATION , *CYTOPLASM , *ACTIN - 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 phosphorylotion of cargo proteins, but the underlying mechanism remains elusive. Myopodin is a dual-comportment, 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 14-3-30 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. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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