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.
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA. jlspence@netscape.net
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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