| First Author | Lavi-Itzkovitz A | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 3 | Pages | e33786 |
| PubMed ID | 22442722 | Mgi Jnum | J:380342 |
| Mgi Id | MGI:6228290 | Doi | 10.1371/journal.pone.0033786 |
| Citation | Lavi-Itzkovitz A, et al. (2012) Functional consequences of necdin nucleocytoplasmic localization. PLoS One 7(3):e33786 |
| abstractText | 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 beta1. 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. |
