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A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif.
Margottin, F; Bour, S P; Durand, H; Selig, L; Benichou, S; Richard, V; Thomas, D; Strebel, K; Benarous, R.
Afiliación
  • Margottin F; CJF 97-03 INSERM, Institut Cochin de Génétique Moléculaire, Université Paris V, Faculté de médecine Cochin, France.
Mol Cell ; 1(4): 565-74, 1998 Mar.
Article en En | MEDLINE | ID: mdl-9660940
HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu and its recruitment to membranes require two phosphoserine residues in Vpu essential for CD4 degradation. In beta TrCP, WD repeats at the C terminus mediate binding to Vpu, and an F box near the N terminus is involved in interaction with Skp1p, a targeting factor for ubiquitin-mediated proteolysis. An F-box deletion mutant of beta TrCP had a dominant-negative effect on Vpu-mediated CD4 degradation. These data suggest that beta TrCP and Skp1p represent components of a novel ER-associated protein degradation pathway that mediates CD4 proteolysis.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos CD4 / VIH-1 / Proteínas de Unión al GTP / Retículo Endoplásmico / Proteínas Reguladoras y Accesorias Virales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 1998 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos CD4 / VIH-1 / Proteínas de Unión al GTP / Retículo Endoplásmico / Proteínas Reguladoras y Accesorias Virales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 1998 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos