TY - JOUR
T1 - Senp1 Is Essential for Desumoylating Sumo1-Modified Proteins but Dispensable for Sumo2 and Sumo3 Deconjugation in the Mouse Embryo
AU - Sharma, Prashant
AU - Yamada, Satoru
AU - Lualdi, Margaret
AU - Dasso, Mary
AU - Kuehn, Michael R.
N1 - Funding Information:
We thank Dr. Lionel Feigenbaum and the Transgenic Mouse Model Laboratory for generation of germline chimeric mice from XG001 ES cells; Dr. Stephen Goff for HA-Sumo retroviral vectors; Dr. Jadranka Loncarek for assistance with quantification; and Drs. Ira Daar and Allan Weissman for comments on the manuscript. This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services and nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
PY - 2013/5/30
Y1 - 2013/5/30
N2 - 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. Invitro, 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 invivo isstill 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.
AB - 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. Invitro, 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 invivo isstill 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.
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U2 - 10.1016/j.celrep.2013.04.016
DO - 10.1016/j.celrep.2013.04.016
M3 - Article
C2 - 23684609
AN - SCOPUS:84878616564
VL - 3
SP - 1640
EP - 1650
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -