SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis.
SUMOylation is essential for cell-cycle regulation in invertebrates; however, its functions during the mammalian cell cycle are largely uncharacterized. Mammals express three SUMO paralogs: SUMO-1, SUMO-2, and SUMO-3 (SUMO-2 and SUMO-3 are 96% identical and referred to as SUMO-2/3). We found that SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells. Consistent with this, global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. CENP-E was found to be modified specifically by SUMO-2/3 and to possess SUMO-2/3 polymeric chain-binding activity essential for kinetochore localization. Our findings indicate that SUMOylation is a key regulator of the mammalian cell cycle, with SUMO-1 and SUMO-2/3 modification of different proteins regulating distinct processes.
Zhang
Xiang-Dong
XD
Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Goeres
Jacqueline
J
Zhang
Hong
H
Yen
Tim J
TJ
Porter
Andrew C G
AC
Matunis
Michael J
MJ
D002453:Cell Cycle / Q000502:physiology*; D002503:Centromere / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D026942:DNA Topoisomerases / Q000378:metabolism; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D008938:Mitosis / Q000502:physiology*; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014452:Ubiquitins; C068688:centromere protein E; D003546:Cysteine Endopeptidases; C501833:SENP2 protein, human; D026942:DNA Topoisomerases