title: Ubiquitin ligase Ufd2 is required for efficient degradation of Mps1 kinase.
abstract: Ufd2 is a U-box-containing ubiquitylation enzyme that promotes ubiquitin chain assembly on substrates. The physiological function of Ufd2 remains poorly understood. Here, we show that ubiquitylation and degradation of the cell cycle kinase Mps1, a known target of the anaphase-promoting complex E3, require Ufd2 enzyme. Yeast cells lacking UFD2 exhibit altered chromosome stability and several spindle-related phenotypes, expanding the biological function of Ufd2. We demonstrate that Ufd2-mediated Mps1 degradation is conserved in humans. Our results underscore the significance of Ufd2 in proteolysis and further suggest that Ufd2-like enzymes regulate far more substrates than previously envisioned.
authors: Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245.
authors: Chang
authors: C
authors: Liu
authors: Banting and Best Department of Medical Research, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada.
authors: Dewald
authors: D
authors: van Dyk
authors: Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245.
authors: Vitnary
authors: V
authors: Choe
authors: Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245; State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China.
authors: Jing
authors: J
authors: Yan
authors: Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, and.
authors: Shubhra
authors: S
authors: Majumder
authors: Banting and Best Department of Medical Research, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada.
authors: Michael
authors: M
authors: Costanzo
authors: Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245.
authors: Xin
authors: X
authors: Bao
authors: Banting and Best Department of Medical Research, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada.
authors: Charles
authors: C
authors: Boone
authors: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China.
authors: Keke
authors: K
authors: Huo
authors: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309.
authors: Mark
authors: M
authors: Winey
authors: Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, and.
authors: Harold
authors: H
authors: Fisk
authors: Banting and Best Department of Medical Research, Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5G 1L6, Canada.
authors: Brenda
authors: B
authors: Andrews
authors: Institute of Biotechnology, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, Texas 78245. Electronic address: raoh@uthscsa.edu.
authors: Hai
authors: H
authors: Rao
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008297:Male; D051379:Mice; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D059748:Proteolysis; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D037102:Lectins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human; C093416:MPS1 protein, S cerevisiae; C114683:UFD2 protein, S cerevisiae