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In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome.
Tsuchiya, Hikaru; Ohtake, Fumiaki; Arai, Naoko; Kaiho, Ai; Yasuda, Sayaka; Tanaka, Keiji; Saeki, Yasushi.
Afiliação
  • Tsuchiya H; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
  • Ohtake F; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
  • Arai N; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
  • Kaiho A; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
  • Yasuda S; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
  • Tanaka K; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan. Electronic address: tanaka-kj@igakuken.or.jp.
  • Saeki Y; Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan. Electronic address: saeki-ys@igakuken.or.jp.
Mol Cell ; 66(4): 488-502.e7, 2017 May 18.
Article em En | MEDLINE | ID: mdl-28525741
Ubiquitin-binding domain (UBD) proteins regulate numerous cellular processes, but their specificities toward ubiquitin chain types in cells remain obscure. Here, we perform a quantitative proteomic analysis of ubiquitin linkage-type selectivity of 14 UBD proteins and the proteasome in yeast. We find that K48-linked chains are directed to proteasomal degradation through selectivity of the Cdc48 cofactor Npl4. Mutating Cdc48 results in decreased selectivity, and lacking Rad23/Dsk2 abolishes interactions between ubiquitylated substrates and the proteasome. Among them, only Npl4 has K48 chain specificity in vitro. Thus, the Cdc48 complex functions as a K48 linkage-specifying factor upstream of Rad23/Dsk2 for proteasomal degradation. On the other hand, K63 chains are utilized in endocytic pathways, whereas both K48 and K63 chains are found in the MVB and autophagic pathways. Collectively, our results provide an overall picture of the ubiquitin network via UBD proteins and identify the Cdc48-Rad23/Dsk2 axis as a major route to the proteasome.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / Ubiquitinas / Adenosina Trifosfatases / Proteínas de Ciclo Celular / Proteínas de Saccharomyces cerevisiae / Ubiquitina / Complexo de Endopeptidases do Proteassoma / Proteínas de Ligação a DNA / Ubiquitinação Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / Ubiquitinas / Adenosina Trifosfatases / Proteínas de Ciclo Celular / Proteínas de Saccharomyces cerevisiae / Ubiquitina / Complexo de Endopeptidases do Proteassoma / Proteínas de Ligação a DNA / Ubiquitinação Tipo de estudo: Prognostic_studies Idioma: En Revista: Mol Cell Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Japão