title: Involvement of Bag6 and the TRC pathway in proteasome assembly.
abstract: The 26S proteasome has an elaborate structure, consisting of 33 different subunits that form the 20S core particle capped by the 19S regulatory particle on either end. Several chaperones that are dedicated to the accurate assembly of this protease complex have been identified, but the mechanisms underlying proteasome biogenesis remain unexplored so far. Here we report that core particle assembly becomes less efficient if the TRC pathway, which mediates insertion of tail-anchored proteins, is defective. We demonstrate that Bag6, a protein in the TRC pathway that is also responsible for the degradation of mislocalized proteins, is not only involved in core particle assembly but also has a key role in efficient regulatory particle assembly by directly associating with precursor regulatory particles. These findings indicate that proteasome assembly is not solely mediated by dedicated chaperones but also depends on general chaperones that preserve protein homeostasis.
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akahane
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sahara
authors.forename: Hideki
authors.initials: H
authors.lastname: Yashiroda
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D053898:Biosynthetic Pathways; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008322:Mammals / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D021122:Protein Subunits; D034741:RNA, Small Interfering / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: C092009:BAG6 protein, human; D018832:Molecular Chaperones; C114476:PSMD9 protein, human; D021122:Protein Subunits; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; C064757:PSMC3 protein, human