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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Bone Marrow Cells / metabolism
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Candida albicans / genetics*
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Candida albicans / metabolism
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Gene Expression Regulation, Fungal*
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Humans
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Lectins / chemistry
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Male
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Mice
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Mitosis
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / metabolism*
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Proteolysis
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Saccharomyces cerevisiae Proteins / metabolism*
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Ubiquitin / chemistry
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Ubiquitin-Conjugating Enzymes / metabolism*
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Ubiquitin-Protein Ligase Complexes / chemistry
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Ubiquitin-Protein Ligases / chemistry
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Ubiquitin-Protein Ligases / metabolism*
Substances
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Cell Cycle Proteins
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Lectins
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Saccharomyces cerevisiae Proteins
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Ubiquitin
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Ubiquitin-Conjugating Enzymes
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Ubiquitin-Protein Ligases
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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TTK protein, human
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MPS1 protein, S cerevisiae
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UFD2 protein, S cerevisiae