Reference - Detail
|Author||Nakatsukasa K, Brodsky JL, Kamura T.|
|Title||A stalled retrotranslocation complex reveals physical linkage between substrate recognition and proteasomal degradation during ER-associated degradation.|
|Journal||Mol. Biol. Cell|
During endoplasmic reticulum-associated degradation (ERAD), misfolded lumenal and membrane proteins in the ER are recognized by the transmembrane Hrd1 ubiquitin ligase complex and retrotranslocated to the cytosol for ubiquitination and degradation. Although substrates are believed to be delivered to the proteasome only after the ATPase Cdc48p/p97 acts, there is limited knowledge about how the Hrd1 complex coordinates with Cdc48p/p97 and the proteasome to orchestrate substrate recognition and degradation. Here we provide evidence that inactivation of Cdc48p/p97 stalls retrotranslocation and triggers formation of a complex that contains the 26S proteasome, Cdc48p/p97, ubiquitinated substrates, select components of the Hrd1 complex, and the lumenal recognition factor, Yos9p. We propose that the actions of Cdc48p/p97 and the proteasome are tightly coupled during ERAD. Our data also support a model in which the Hrd1 complex links substrate recognition and degradation on opposite sides of the ER membrane.
|MeSH||Adenosine Triphosphatases / deficiency Adenosine Triphosphatases / genetics* Carrier Proteins / genetics Carrier Proteins / metabolism Cell Cycle Proteins / deficiency Cell Cycle Proteins / genetics* Cytoplasm / metabolism Endoplasmic Reticulum / genetics* Endoplasmic Reticulum / metabolism Endoplasmic Reticulum-Associated Degradation Gene Expression Regulation, Fungal* Intracellular Membranes / metabolism Proteasome Endopeptidase Complex / metabolism* Protein Folding Protein Transport Saccharomyces cerevisiae / genetics* Saccharomyces cerevisiae / metabolism Saccharomyces cerevisiae Proteins / genetics* Saccharomyces cerevisiae Proteins / metabolism Signal Transduction Ubiquitin / genetics Ubiquitin / metabolism Ubiquitin-Protein Ligases / genetics* Ubiquitin-Protein Ligases / metabolism Ubiquitination Valosin Containing Protein|
|WOS Category||CELL BIOLOGY|