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Subcellular localization

basal body, Mitochondria

Functional category

• Motors (dynein/kinesin)
• Ciliary assembly/disassembly
• Cilia–cytoskeleton/adhesion links

Function

FBXW5 regulates ciliogenesis by controlling the basal body-associated abundance of kinesin-13 microtubule depolymerases, including MCAK/KIF2C, during cell cycle progression. Using comprehensive screening on protein microarrays, we identified 161 candidate substrates of the multi-subunit ubiquitin E3 ligase SCFFbxw5 , including the kinesin-13 member Kif2c/MCAK. In vitro reconstitution assays demonstrate that MCAK and its closely related orthologs Kif2a and Kif2b become efficiently polyubiquitylated by neddylated SCFFbxw5 and Cdc34, without requiring preceding modifications. In cells, SCFFbxw5 targets MCAK for proteasomal degradation predominantly during G2 . While this seems largely dispensable for mitotic progression, loss of Fbxw5 leads to increased MCAK levels at basal bodies and impairs ciliogenesis in the following G1 /G0 , which can be rescued by concomitant knockdown of MCAK, Kif2a or Kif2b. We thus propose a novel regulatory event of ciliogenesis that begins already within the G2 phase of the preceding cell cycle(34368969).