RRC ID 48047
著者 Tsuchiya H, Ohtake F, Arai N, Kaiho A, Yasuda S, Tanaka K, Saeki Y.
タイトル In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome.
ジャーナル Mol Cell
Abstract 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.
巻・号 66(4)
ページ 488-502.e7
公開日 2017-5-18
DOI 10.1016/j.molcel.2017.04.024
PII S1097-2765(17)30309-X
PMID 28525741
MeSH Adenosine Triphosphatases / genetics Adenosine Triphosphatases / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Endocytosis Endosomal Sorting Complexes Required for Transport / genetics Endosomal Sorting Complexes Required for Transport / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Nucleocytoplasmic Transport Proteins / genetics Nucleocytoplasmic Transport Proteins / metabolism Proteasome Endopeptidase Complex / drug effects Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism* Proteasome Inhibitors / pharmacology Protein Binding Protein Interaction Domains and Motifs Proteolysis Saccharomyces cerevisiae / drug effects Saccharomyces cerevisiae / enzymology* Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism* Time Factors Ubiquitin / metabolism* Ubiquitination* / drug effects Ubiquitins / genetics Ubiquitins / metabolism* Valosin Containing Protein
IF 15.584
引用数 37
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
酵母 BYP7430 (pMK151) BYP7431 (pMK153) pNHK36: OsTIR1 cDNA