title: SUSP1 antagonizes formation of highly SUMO2/3-conjugated species.
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.
authors.affiliation: Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Debaditya
authors.initials: D
authors.lastname: Mukhopadhyay
authors.forename: Ferhan
authors.initials: F
authors.lastname: Ayaydin
authors.forename: Nagamalleswari
authors.initials: N
authors.lastname: Kolli
authors.forename: Shyh-Han
authors.initials: SH
authors.lastname: Tan
authors.forename: Tadashi
authors.initials: T
authors.lastname: Anan
authors.forename: Ai
authors.initials: A
authors.lastname: Kametaka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Azuma
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilkinson
authors.forename: Mary
authors.initials: M
authors.lastname: Dasso
mesh_terms: D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D010450:Endopeptidases / Q000145:classification; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D010802:Phylogeny; D000071156:Promyelocytic Leukemia Protein; D025841:Small Ubiquitin-Related Modifier Proteins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism; D014452:Ubiquitins / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C070576:PML protein, human; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human; C477008:SENP8 protein, human