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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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