title: Eukaryotic cells producing ribosomes deficient in Rpl1 are hypersensitive to defects in the ubiquitin-proteasome system.
abstract: It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Kerri B
authors.initials: KB
authors.lastname: McIntosh
authors.forename: Arpita
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Ian M
authors.initials: IM
authors.lastname: Willis
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Warner
mesh_terms: D015153:Blotting, Western; D005057:Eukaryotic Cells / Q000378:metabolism; D017353:Gene Deletion; D057895:Haploinsufficiency; D007976:Leupeptins / Q000494:pharmacology; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D054683:Ribosome Subunits, Large, Eukaryotic / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D007976:Leupeptins; D061988:Proteasome Inhibitors; D012335:RNA, Ribosomal; C569832:RPL1B protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; C028546:ribosomal protein L1; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde