Redundant Roles of Rpn10 and Rpn13 in Recognition of Ubiquitinated Proteins and Cellular Homeostasis

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At least two major ubiquitin receptor subunits that directly capture ubiquitin chains have been identified in the proteasome: Rpn10 and Rpn13. Analyses in Saccharomyces cerevisiae have suggested only a modest role of Rpn10 and Rpn13 in the recruitment of ubiquitinated proteins, as double deletion of Rpn10 and Rpn13 causes very mild phenotypes. Considering that ubiquitin recognition is an essential process for protein degradation by the proteasome and that failure in degradation of ubiquitinated proteins leads to human diseases such as neurodegeneration, it is important to evaluate the role of Rpn10 and Rpn13 in mammals. Liver-specific deletion of either Rpn10 or Rpn13 showed modest impairment, but simultaneous loss of both Rpn10 and Rpn13 caused severe liver injury accompanied by massive accumulation of ubiquitin conjugates and failure in recruiting mHR23B and ubiquilin/Plic-1 and -4 proteins, which deliver ubiquitinated proteins to the proteasome. Our findings indicate that the largely redundant roles of Rpn10 and Rpn13 in ubiquitin recognition and recruitment of mHR23B and ubiquilin/Plic-1 and -4 are essential for cellular homeostasis in mammals and should provide information for understanding the mechanism of ubiquitin recognition by the 26S proteasome in mammals and for development of therapeutic agents targeting protein degradation.

Vyšlo v časopise: Redundant Roles of Rpn10 and Rpn13 in Recognition of Ubiquitinated Proteins and Cellular Homeostasis. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005401
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005401

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