functional consequences of necdin nucleocytoplasmic localization功能的后果necdin核质本地化.pdfVIP

functional consequences of necdin nucleocytoplasmic localization功能的后果necdin核质本地化.pdf

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functional consequences of necdin nucleocytoplasmic localization功能的后果necdin核质本地化

Functional Consequences of Necdin Nucleocytoplasmic Localization 1 1 1 1 2 Anat Lavi-Itzkovitz , Marianna Tcherpakov , Zehava Levy , Shalev Itzkovitz , Francoise Muscatelli , Mike Fainzilber1* ´ ´ 1 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel, 2 Institut de Neurobiologie de la Mediterranee, INSERM U901, Parc Scientifique de Luminy BP 13, Marseille, France Abstract Background: Necdin, a MAGE family protein expressed primarily in the nervous system, has been shown to interact with both nuclear and cytoplasmic proteins, but the mechanism of its nucleocytoplasmic transport are unknown. Methodology/Principal Findings: We carried out a large-scale interaction screen using necdin as a bait in the yeast RRS system, and found a wide range of potential interactors with different subcellular localizations, including over 60 new candidates for direct binding to necdin. Integration of these interactions into a comprehensive network revealed a number of coherent interaction modules, including a cytoplasmic module connecting to necdin through huntingtin-associated protein 1 (Hap1), dynactin and hip-1 protein interactor (Hippi); a nuclear P53 and Creb-binding-protein (Crebbp) module, connecting through Crebbp and WW domain-containing transcription regulator protein 1 (Wwtr1); and a nucleocytoplasmic transport module, connecting through transportins 1 and 2. We validated the necdin-transportin1 interaction and characterized a sequence motif in necdin that modulates karyopherin interaction. Surprisingly, a D234P necd

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