The Slow Wallerian Degeneration Protein, WldS, Binds Directly to VCP/p97 and Partially Redistributes It within the NucleusD?
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The Slow Wallerian Degeneration Protein, WldS, Binds Directly to VCP/p97 and Partially Redistributes It within the NucleusD?
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| Id. |
5313261 |
| Idioma |
inglés
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| Titulo |
The Slow Wallerian Degeneration Protein, WldS, Binds Directly to VCP/p97 and Partially Redistributes It within the NucleusD? |
| Autor(es) |
Laser, Heike Conforti, Laura Morreale, Giacomo Mack, Till G.M. Heyer, Molly Haley, Jane E. Wishart, Thomas M. Beirowski, Bogdan Walker, Simon A. Haase, Georg Celik, Arzu Adalbert, Robert Wagner, Diana Grumme, Daniela Ribchester, Richard R. Plomann, Markus Coleman, Michael P. |
| Localización |
http://www.pubmedcentral.gov/articlerender.fcgi?artid=1382299
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| Versión |
1.0 |
| Estado |
Final
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| Descripción |
Slow Wallerian degeneration (WldS) mutant mice express a chimeric nuclear protein that protects sick or injured axons from degeneration. The C-terminal region, derived from NAD+ synthesizing enzyme Nmnat1, is reported to confer neuroprotection in vitro. However, an additional role for the N-terminal 70 amino acids (N70), derived from multiubiquitination factor Ube4b, has not been excluded. In wild-type Ube4b, N70 is part of a sequence essential for ubiquitination activity but its role is not understood. We report direct binding of N70 to valosin-containing protein (VCP; p97/Cdc48), a protein with diverse cellular roles including a pivotal role in the ubiquitin proteasome system. Interaction with WldS targets VCP to discrete intranuclear foci where ubiquitin epitopes can also accumulate. WldS lacking its N-terminal 16 amino acids (N16) neither binds nor redistributes VCP, but continues to accumulate in intranuclear foci, targeting its intrinsic NAD+ synthesis activity to these same foci. Wild-type Ube4b also requires N16 to bind VCP, despite a more C-terminal binding site in invertebrate orthologues. We conclude that N-terminal sequences of WldS protein influence the intranuclear location of both ubiquitin proteasome and NAD+ synthesis machinery and that an evolutionary recent sequence mediates binding of mammalian Ube4b to VCP. |
| Palabras clave |
Articles |
| Tipo de recurso |
Text
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| Tipo de Interactividad |
Expositivo
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| Nivel de Interactividad |
muy bajo
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| Audiencia |
Estudiante
Profesor
Autor
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| Estructura |
Atomic |
| Coste |
no
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| Copyright |
sí
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Copyright © 2006, The American Society for Cell Biology |
| Requerimientos técnicos |
Browser: Any |
| Fecha de contribución |
01-dic-2006 |
| Contacto |
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