SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL

J Cell Biol. 2019 Jul 1;218(7):2185-2197. doi: 10.1083/jcb.201803041. Epub 2019 Jun 13.


In mammals, centrioles participate in brain development, and human mutations affecting centriole duplication cause microcephaly. Here, we identify a role for the mammalian homologue of yeast SFI1, involved in the duplication of the yeast spindle pole body, as a critical regulator of centriole duplication in mammalian cells. Mammalian SFI1 interacts with USP9X, a deubiquitylase associated with human syndromic mental retardation. SFI1 localizes USP9X to the centrosome during S phase to deubiquitylate STIL, a critical regulator of centriole duplication. USP9X-mediated deubiquitylation protects STIL from degradation. Consistent with a role for USP9X in stabilizing STIL, cells from patients with USP9X loss-of-function mutations have reduced STIL levels. Together, these results demonstrate that SFI1 is a centrosomal protein that localizes USP9X to the centrosome to stabilize STIL and promote centriole duplication. We propose that the USP9X protection of STIL to facilitate centriole duplication underlies roles of both proteins in human neurodevelopment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics*
  • Centrioles / genetics
  • Centrioles / ultrastructure
  • Centrosome / ultrastructure
  • Female
  • Fibroblasts / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Microcephaly / genetics*
  • Microcephaly / pathology
  • Microscopy, Electron
  • Mutation
  • Neurodevelopmental Disorders / genetics
  • Proteolysis
  • Ubiquitin Thiolesterase / genetics*


  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • STIL protein, human
  • Sfi1 protein, human
  • USP9X protein, human
  • Ubiquitin Thiolesterase