Abstract
Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green fluorescent protein (EGFP) fusions to individual SUMO paralogues caused redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia (PML) bodies. Further analysis suggested that this change resulted primarily from a deficit of SUMO2/3-deconjugation activity. Under these circumstances, PML bodies became enlarged and increased in number. We did not observe a comparable redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong paralogue bias toward SUMO2/3 and that it acts preferentially on substrates containing three or more SUMO2/3 moieties. Together, our findings argue that SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3 species that is critical for PML body maintenance.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cysteine Endopeptidases / analysis
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Cysteine Endopeptidases / pharmacology
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Cysteine Endopeptidases / physiology*
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Endopeptidases / classification
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HeLa Cells
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Humans
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Multiprotein Complexes / analysis
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Multiprotein Complexes / antagonists & inhibitors
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Multiprotein Complexes / metabolism
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / metabolism
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism
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Phylogeny
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Promyelocytic Leukemia Protein
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Small Ubiquitin-Related Modifier Proteins / analysis
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Small Ubiquitin-Related Modifier Proteins / antagonists & inhibitors*
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Small Ubiquitin-Related Modifier Proteins / metabolism
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Substrate Specificity
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Transcription Factors / chemistry
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Transcription Factors / metabolism
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / metabolism
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Ubiquitins / analysis
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Ubiquitins / antagonists & inhibitors*
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Ubiquitins / metabolism
Substances
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Multiprotein Complexes
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Neoplasm Proteins
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Nuclear Proteins
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Promyelocytic Leukemia Protein
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SUMO2 protein, human
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SUMO3 protein, human
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Small Ubiquitin-Related Modifier Proteins
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Transcription Factors
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Tumor Suppressor Proteins
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Ubiquitins
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PML protein, human
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Endopeptidases
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Cysteine Endopeptidases
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SENP6 protein, human
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SENP8 protein, human