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dc.contributor.authorFaul, Christian Herbert
dc.date.accessioned2018-07-12T17:33:33Z
dc.date.available2018-07-12T17:33:33Z
dc.date.issued2005
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 66-07, Section: B, page: 3504.;Advisors: Peter Mundel.
dc.identifier.urihttp://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3181634
dc.identifier.urihttps://hdl.handle.net/20.500.12202/789
dc.description.abstract14-3-3 proteins are phospho-serine/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 or the nucleus or mediate their nuclear export. So far no role for 14-3-3 in mediating nuclear import has been described. Myopodin is a dual compartment actin-bundling protein with tumor suppressor function in human bladder cancer. In muscle cells, myopodin redistributes between the nucleus and cytoplasm in a differentiation-dependent and stress-induced fashion. Here we show that importin a binding and subsequent nuclear import of myopodin is regulated by serine/threonine phosphorylation dependent binding of myopodin to 14-3-3. Furthermore, we establish that protein kinase A (PKA) and the calcium/calmodulin-dependent kinase II (CaMKII) phosphorylate the two 14-3-3 binding motifs of myopodin, thereby mediating the 14-3-3 binding and subsequent nuclear import of myopodin in myoblasts. In contrast, the protein phosphatase calcineurin dephosphorylates myopodin and abrogates the interaction between myopodin and 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 phosphorylation dependent nuclear import of nuclear localization signal containing cargo proteins.
dc.publisherProQuest Dissertations & Theses
dc.subjectCellular biology.
dc.titlePhosphorylation-dependent regulation of nuclear import by 14-3-3
dc.typeDissertation


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