title: Senp1 is essential for desumoylating Sumo1-modified proteins but dispensable for Sumo2 and Sumo3 deconjugation in the mouse embryo.
abstract: Posttranslational modification with small ubiquitin-like modifier (Sumo) regulates numerous cellular and developmental processes. Sumoylation is dynamic with deconjugation by Sumo-specific proteases (Senps) regulating steady-state levels. Different Senps are found in distinct subcellular domains, which may limit their deconjugation activity to colocalizing Sumo-modified proteins. In vitro, Senps can discriminate between the different Sumo paralogs: Sumo1 versus the highly related Sumo2 and Sumo3 (Sumo2/3), which can form poly-Sumo chains. However, a full understanding of Senp specificity in vivo is still lacking. Here, using biochemical and genetic approaches, we establish that Senp1 has an essential, nonredundant function to desumoylate Sumo1-modified proteins during mouse embryonic development. Senp1 specificity for Sumo1 conjugates represents an intrinsic function and not simply a product of colocalization. In contrast, Senp1 has only a limited role in Sumo2/3 desumoylation, although it may regulate Sumo1-mediated termination of poly-Sumo2/3 chains.
authors.affiliation: Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.forename: Margaret
authors.initials: M
authors.lastname: Lualdi
authors.forename: Mary
authors.initials: M
authors.lastname: Dasso
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kuehn
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; C117908:Sumo3 protein, mouse; D014452:Ubiquitins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C501974:Senp1 protein, mouse; C439066:Senp2 protein, mouse