Loss of SUMO1 in mice affects RanGAP1 localization and formation of PML nuclear bodies, but is not lethal as it can be compensated by SUMO2 or SUMO3.
Conjugation of the small ubiquitin-like modifier (SUMO) to target proteins regulates numerous biological processes and has been implicated in tumorigenesis and metastasis. The three SUMO isoforms in vertebrates, SUMO1 and the highly similar SUMO2 and SUMO3, can be conjugated to unique as well as overlapping subsets of target proteins. Yet, it is still not clear whether roles for each family member are distinct or whether redundancy exists. Here we describe a mutant mouse line that completely lacks SUMO1, but surprisingly is viable and lacks any overt phenotype. Our study points to compensatory utilization of SUMO2 and/or SUMO3 for sumoylation of SUMO1 targets. The ability of SUMO isoforms to substitute for one another has important implications for rational targeting of the SUMO pathway.
Evdokimov
Evgenij
E
Laboratory of Protein Dynamics and Signaling, National Cancer Institute, National Institutes of Health, NCI-Frederick, Frederick, MD 21702, USA.
Sharma
Prashant
P
Lockett
Stephen J
SJ
Lualdi
Margaret
M
Kuehn
Michael R
MR
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; C085844:Rangap1 protein, mouse; D025842:SUMO-1 Protein; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; C117908:Sumo3 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins