title: A conserved quality-control pathway that mediates degradation of unassembled ribosomal proteins.
abstract: Overproduced yeast ribosomal protein (RP) Rpl26 fails to assemble into ribosomes and is degraded in the nucleus/nucleolus by a ubiquitin-proteasome system quality control pathway comprising the E2 enzymes Ubc4/Ubc5 and the ubiquitin ligase Tom1. tom1 cells show reduced ubiquitination of multiple RPs, exceptional accumulation of detergent-insoluble proteins including multiple RPs, and hypersensitivity to imbalances in production of RPs and rRNA, indicative of a profound perturbation to proteostasis. Tom1 directly ubiquitinates unassembled RPs primarily via residues that are concealed in mature ribosomes. Together, these data point to an important role for Tom1 in normal physiology and prompt us to refer to this pathway as ERISQ, for excess ribosomal protein quality control. A similar pathway, mediated by the Tom1 homolog Huwe1, restricts accumulation of overexpressed hRpl26 in human cells. We propose that ERISQ is a key element of the quality control machinery that sustains protein homeostasis and cellular fitness in eukaryotes.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
authors.forename: Min-Kyung
authors.identifier: 0000-0002-0513-6834
authors.initials: MK
authors.lastname: Sung
authors.affiliation: Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institue, California Institute of Technology, Pasadena, United States.
authors.forename: Tanya R
authors.initials: TR
authors.lastname: Porras-Yakushi
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Reitsma
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, United States.
authors.forename: Ferdinand M
authors.initials: FM
authors.lastname: Huber
authors.affiliation: Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institue, California Institute of Technology, Pasadena, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sweredoski
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, United States.
authors.forename: André
authors.initials: A
authors.lastname: Hoelz
authors.affiliation: Proteome Exploration Laboratory, Division of Biology and Biological Engineering, Beckman Institue, California Institute of Technology, Pasadena, United States.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hess
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.|Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States.
authors.forename: Raymond J
authors.identifier: 0000-0002-3671-9354
authors.initials: RJ
authors.lastname: Deshaies
mesh_terms: D017353:Gene Deletion; D053858:Metabolic Networks and Pathways; D059748:Proteolysis; D011786:Quality Control; D012269:Ribosomal Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: C489218:RPL26A protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C489270:UBC5 protein, S cerevisiae; C501306:Ubc4 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; C502830:HUWE1 protein, human; C115246:TOM1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases
keywords: S. cerevisiae; biochemistry; cell biology; human; protein quality control; ribosomal protein; ubiquitin-proteasome system