Cell cycle-regulated modification of the ribosome by a variant multiubiquitin chain.
Ubiquitin is ligated to L28, a component of the large ribosomal subunit, to form the most abundant ubiquitin-protein conjugate in S. cerevisiae. The human ortholog of L28 is also ubiquitinated, indicating that this modification is highly conserved in evolution. During S phase of the yeast cell cycle, L28 is strongly ubiquitinated, while reduced levels of L28 ubiquitination are observed in G1 cells. L28 ubiquitination is inhibited by a Lys63 to Arg substitution in ubiquitin, indicating that L28 is modified by a variant, Lys63-linked multiubiquitin chain. The K63R mutant of ubiquitin displays defects in ribosomal function in vivo and in vitro, including a dramatic sensitivity to translational inhibitors. L28, like other ribosomal proteins, is metabolically stable. Therefore, these data suggest a regulatory role for multiubiquitin chains that is reversible and does not function to target the acceptor protein for degradation.
Spence
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Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. jlspence@netscape.net
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Dittmar
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Sherman
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Karin
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D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001704:Biopolymers / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002461:Cell Line, Transformed; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D015636:Magnesium Chloride / Q000494:pharmacology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011132:Polyribosomes / Q000378:metabolism; D025821:Polyubiquitin; D014176:Protein Biosynthesis; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D001704:Biopolymers; C489321:RPL28 protein, S cerevisiae; C489320:RPL28 protein, human; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C039913:ribosomal protein S80; D015636:Magnesium Chloride; D025821:Polyubiquitin; D001120:Arginine; D008239:Lysine