title: A ubiquitin-interacting motif protects polyubiquitinated Met4 from degradation by the 26S proteasome.
abstract: Covalent attachment of ubiquitin to proteins regulates a host of cellular events by proteolysis dependent and independent mechanisms. A variety of protein domains that bind non-covalently to ubiquitin have been described and functionally linked to diverse cellular processes. Overall, however, the understanding and knowledge of the mechanisms by which ubiquitin-binding domains (UBDs) regulate these processes is limited. Here, we describe identification of a UBD in the yeast transcription factor Met4. Met4 activity, but not its stability, is regulated by polyubiquitination. We found that the UBD restricts the length of the polyubiquitin chain that is assembled on Met4, and prevents proteasomal recognition and degradation of polyubiquitinated Met4. Inactivation of the UBD allowed synthesis of longer ubiquitin chains on Met4 and transformed the normally stable polyubiquitinated Met4 into a short-lived protein. Our results demonstrate a function for UBDs in ubiquitin-chain synthesis and regulation of protein degradation.
authors.affiliation: University of California Irvine, Department of Biological Chemistry, School of Medicine, 240D Med Sci I, Irvine, CA 92697-1700, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Flick
authors.forename: Shahri
authors.initials: S
authors.lastname: Raasi
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: James L
authors.initials: JL
authors.lastname: Yen
authors.forename: Peter
authors.initials: P
authors.lastname: Kaiser
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D003547:Cysteine Synthase; D004268:DNA-Binding Proteins / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics; D025821:Polyubiquitin / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C073675:MET4 protein, S cerevisiae; C106765:Met32 protein, S cerevisiae; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025821:Polyubiquitin; D003547:Cysteine Synthase; C103381:MET17 protein, S cerevisiae; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008239:Lysine