title: Redundant Roles of Rpn10 and Rpn13 in Recognition of Ubiquitinated Proteins and Cellular Homeostasis.
abstract: Intracellular proteins tagged with ubiquitin chains are targeted to the 26S proteasome for degradation. The two subunits, Rpn10 and Rpn13, function as ubiquitin receptors of the proteasome. However, differences in roles between Rpn10 and Rpn13 in mammals remains to be understood. We analyzed mice deficient for Rpn13 and Rpn10. Liver-specific deletion of either Rpn10 or Rpn13 showed only modest impairment, but simultaneous loss of both caused severe liver injury accompanied by massive accumulation of ubiquitin conjugates, which was recovered by re-expression of either Rpn10 or Rpn13. We also found that mHR23B and ubiquilin/Plic-1 and -4 failed to bind to the proteasome in the absence of both Rpn10 and Rpn13, suggesting that these two subunits are the main receptors for these UBL-UBA proteins that deliver ubiquitinated proteins to the proteasome. Our results indicate that Rpn13 mostly plays a redundant role with Rpn10 in recognition of ubiquitinated proteins and maintaining homeostasis in Mus musculus.
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hamazaki
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shoshiro
authors.initials: S
authors.lastname: Hirayama
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000293:injuries; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D025801:Ubiquitin / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C411807:Adrm1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490781:Psmd4 protein, mouse; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C499250:Rad23b protein, mouse; C538987:UBQLN1 protein, mouse; D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease