Ubiquitin-proteasome system controls ciliogenesis at the initial step of axoneme extension

Nat Commun. 2014 Oct 1;5:5081. doi: 10.1038/ncomms6081.


Primary cilia are microtubule-based sensory organelles that organize numerous key signals during developments and tissue homeostasis. Ciliary microtubule doublet, named axoneme, is grown directly from the distal end of mother centrioles through a multistep process upon cell cycle exit; however, the instructive signals that initiate these events are poorly understood. Here we show that ubiquitin-proteasome machinery removes trichoplein, a negative regulator of ciliogenesis, from mother centrioles and thereby causes Aurora-A inactivation, leading to ciliogenesis. Ciliogenesis is blocked if centriolar trichoplein is stabilized by treatment with proteasome inhibitors or by expression of non-ubiquitylatable trichoplein mutant (K50/57R). Started from two-stepped global E3 screening, we have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Axoneme / enzymology*
  • Axoneme / metabolism*
  • Centrioles / enzymology
  • Centrioles / metabolism*
  • Cilia / enzymology
  • Cilia / genetics
  • Cilia / metabolism*
  • Cullin Proteins / genetics
  • Cullin Proteins / metabolism
  • Humans
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Ubiquitin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • CUL3 protein, human
  • Cullin Proteins
  • KCTD17 protein, human
  • Ubiquitin
  • Proteasome Endopeptidase Complex