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

Devinderjit K. Moudgil, Nathan Westcott, Jakub K. Famulski, Kinjal Patel, Dawn Macdonald, Howard Hang, Gordon K.T. Chan

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish
Pages (from-to)881-896
Number of pages16
JournalJournal of Cell Biology
Issue number7
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 Moudgil et al.

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'A novel role of farnesylation in targeting a mitotic checkpoint protein, human spindly, to kinetochores'. Together they form a unique fingerprint.

Cite this