Centrosomal protein DZIP1 regulates hedgehog signaling by promoting cytoplasmic retention of transcription factor GLI3 and affecting ciliogenesis Academic Article uri icon


MeSH Major

  • Cilia
  • DNA-Binding Proteins
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Signal Transduction


  • The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.

publication date

  • October 11, 2013



  • Academic Article



  • eng

PubMed Central ID

  • PMC3795250

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.492066

PubMed ID

  • 23955340

Additional Document Info

start page

  • 29518

end page

  • 29


  • 288


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