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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 necdin mutant showed enhanced binding to both transportin1 and importin β1. Finally, exclusion of necdin from the nucleus triggered extensive cell death.

Conclusions-Significance

These data suggest that necdin has multiple roles within protein complexes in different subcellular compartments, and indicate that it can utilize multiple karyopherin-dependent pathways to modulate its localization.



Autor: Anat Lavi-Itzkovitz, Marianna Tcherpakov, Zehava Levy, Shalev Itzkovitz, Francoise Muscatelli, Mike Fainzilber

Fuente: http://plos.srce.hr/



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