A novel role of farnesylation in targeting a mitotic checkpoint protein, human Spindly, to kinetochores.

TitleA novel role of farnesylation in targeting a mitotic checkpoint protein, human Spindly, to kinetochores.
Publication TypeJournal Article
Year of Publication2015
JournalThe Journal of cell biology
Volume208
Issue7
Pagination881-96
Date Published2015
ISSN0021-9525
Abstract

Kinetochore (KT) localization of mitotic checkpoint proteins is essential for their function during mitosis. hSpindly KT localization is dependent on the RZZ complex and hSpindly recruits the dynein-dynactin complex to KTs during mitosis, but the mechanism of hSpindly KT recruitment is unknown. Through domain-mapping studies we characterized the KT localization domain of hSpindly and discovered it undergoes farnesylation at the C-terminal cysteine residue. The N-terminal 293 residues of hSpindly are dispensable for its KT localization. Inhibition of farnesylation using a farnesyl transferase inhibitor (FTI) abrogated hSpindly KT localization without affecting RZZ complex, CENP-E, and CENP-F KT localization. We showed that hSpindly is farnesylated in vivo and farnesylation is essential for its interaction with the RZZ complex and hence KT localization. FTI treatment and hSpindly knockdown displayed the same mitotic phenotypes, indicating that hSpindly is a key FTI target in mitosis. Our data show a novel role of lipidation in targeting a checkpoint protein to KTs through protein-protein interaction.

URLhttp://jcb.rupress.org/cgi/pmidlookup?view=long&pmid=25825516
DOI10.1083/jcb.201412085
Short TitleJ Cell Biol
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