Small ubiquitin-related modifier (SUMO) binding determines substrate recognition and paralog-selective SUMO modification.
Small ubiquitin-related modifiers (SUMOs) regulate diverse cellular processes through their covalent attachment to target proteins. Vertebrates express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are approximately 96% identical and referred to as SUMO-2/3). SUMO-1 and SUMO-2/3 are conjugated, at least in part, to unique subsets of proteins and thus regulate distinct cellular pathways. However, how different proteins are selectively modified by SUMO-1 and SUMO-2/3 is unknown. We demonstrate that BLM, the RecQ DNA helicase mutated in Bloom syndrome, is preferentially modified by SUMO-2/3 both in vitro and in vivo. Our findings indicate that non-covalent interactions between SUMO and BLM are required for modification at non-consensus sites and that preferential SUMO-2/3 modification is determined by preferential SUMO-2/3 binding. We also present evidence that sumoylation of a C-terminal fragment of HIPK2 is dependent on SUMO binding, indicating that non-covalent interactions between SUMO and target proteins provide a general mechanism for SUMO substrate selection and possible paralog-selective modification.
Zhu
Jianmei
J
Bloomberg School of Public Health, Department of Biochemistry and Molecular Biology, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Zhu
Shanshan
S
Guzzo
Catherine M
CM
Ellis
Nathan A
NA
Sung
Ki Sa
KS
Choi
Cheol Yong
CY
Matunis
Michael J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D004265:DNA Helicases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D053484:RecQ Helicases; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
C117909:SUMO2 protein, human; C515972:SUMO2 protein, mouse; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; C117908:Sumo3 protein, mouse; D014452:Ubiquitins; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases