Abstract
Protein modification by SUMO and ubiquitin critically impacts genome stability via effectors that "read" their signals using SUMO interaction motifs or ubiquitin binding domains, respectively. A novel mixed SUMO and ubiquitin signal is generated by the SUMO-targeted ubiquitin ligase (STUbL), which ubiquitylates SUMO conjugates. Herein, we determine that the "ubiquitin-selective" segregase Cdc48-Ufd1-Npl4 also binds SUMO via a SUMO interaction motif in Ufd1 and can thus act as a selective receptor for STUbL targets. Indeed, we define key cooperative DNA repair functions for Cdc48-Ufd1-Npl4 and STUbL, thereby revealing a new signaling mechanism involving dual recruitment by SUMO and ubiquitin for Cdc48-Ufd1-Npl4 functions in maintaining genome stability.
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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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism*
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Amino Acid Motifs
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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DNA Repair / physiology
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DNA, Fungal / genetics
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DNA, Fungal / metabolism
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Genomic Instability / physiology*
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Protein Binding
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SUMO-1 Protein / genetics
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SUMO-1 Protein / metabolism*
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Schizosaccharomyces / genetics
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Schizosaccharomyces / metabolism*
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Schizosaccharomyces pombe Proteins / genetics
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Schizosaccharomyces pombe Proteins / metabolism*
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Signal Transduction / physiology
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Ubiquitin / genetics
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Ubiquitin / metabolism*
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination / physiology*
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Valosin Containing Protein
Substances
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Carrier Proteins
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Cell Cycle Proteins
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DNA, Fungal
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Npl4 protein, S pombe
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SUMO-1 Protein
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Schizosaccharomyces pombe Proteins
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Ubiquitin
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Ufd1 protein, S pombe
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Ubiquitin-Protein Ligases
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Adenosine Triphosphatases
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Valosin Containing Protein