title: Enhanced protein degradation by branched ubiquitin chains.
abstract: Posttranslational modification of cell-cycle regulators with ubiquitin chains is essential for eukaryotic cell division. Such chains can be connected through seven lysine residues or the amino terminus of ubiquitin, thereby allowing the assembly of eight homogenous and multiple mixed or branched conjugates. Although functions of homogenous chain types have been described, physiological roles of branched structures are unknown. Here, we report that the anaphase-promoting complex (APC/C) efficiently synthesizes branched conjugates that contain multiple blocks of K11-linked chains. Compared to homogenous chains, the branched conjugates assembled by the APC/C strongly enhance substrate recognition by the proteasome, thereby driving degradation of cell-cycle regulators during early mitosis. Our work, therefore, identifies an enzyme and substrates for modification with branched ubiquitin chains and points to an important role of these conjugates in providing an improved signal for proteasomal degradation.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Meyer
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: mrape@berkeley.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Rape
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D000072379:NIMA-Related Kinases; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D059748:Proteolysis; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
chemical_list: C544962:Ube2S protein, human; D044763:Ubiquitin-Conjugating Enzymes; D064173:Anaphase-Promoting Complex-Cyclosome; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex