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Published 18 February 2002. doi:10.1083/jcb.200110109
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© The Rockefeller University Press, 0021-9525/2002/2/595 $5.00
The Journal of Cell Biology, Volume 156, Number 4, February 18, 2002 595-602

Report

 SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles

Jomon Joseph1, Shyh-Han Tan1, Tatiana S. Karpova2, James G. McNally2 and Mary Dasso1

1 Laboratory of Gene Regulation and Development, National Institute of Child Health and Development
2 Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Address correspondence to Mary Dasso, Laboratory of Gene Regulation and Development, National Institute of Child Health and Development, National Institutes of Health, Building 18T, Room 106, 18 Library Dr., MSC 5431, Bethesda, MD 20892. Tel.: (301) 402-1005. Fax: (301) 402-1323. E-mail: mdasso{at}helix.nih.gov

RanGAP1 was the first documented substrate for conjugation with the ubiquitin-like protein SUMO-1. However, the functional significance of this conjugation has not been fully clarified. We sought to examine RanGAP1 behavior during mitosis. We found that RanGAP1 associates with mitotic spindles and that it is particularly concentrated at foci near kinetochores. Association with kinetochores appeared soon after nuclear envelope breakdown and persisted until late anaphase, but it was lost coincident with nuclear envelope assembly in telophase. A mutant RanGAP1 protein lacking the capacity to be conjugated to SUMO-1 no longer associated with spindles, indicating that conjugation was essential for RanGAP1's mitotic localization. RanBP2, a nuclear pore protein that binds SUMO-1–conjugated RanGAP1 during interphase, colocalized with RanGAP1 on spindles, suggesting that a complex between these two proteins may be involved in mitotic targeting of RanGAP1. This report shows for the first time that SUMO-1 conjugation is required for mitotic localization of RanGAP1, and suggests that a major role of SUMO-1 conjugation to RanGAP1 may be the spatial regulation of the Ran pathway during mitosis.

Key Words: RanGAP1; SUMO-1; kinetochore; Ran; RanBP2


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