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ZFIN ID: ZDB-PUB-160520-3
Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination
Li, T., Fan, J., Blanco-Sánchez, B., Giagtzoglou, N., Lin, G., Yamamoto, S., Jaiswal, M., Chen, K., Zhang, J., Wei, W., Lewis, M.T., Groves, A.K., Westerfield, M., Jia, J., Bellen, H.J.
Date: 2016
Source: PLoS Genetics   12: e1006054 (Journal)
Registered Authors: Blanco, Bernardo, Westerfield, Monte
Keywords: Hedgehog signaling, Cloning, Ubiquitination, Zebrafish, Immunoprecipitation, Eyes, Drosophila melanogaster, Small interfering RNAs
MeSH Terms:
  • Animals
  • Drosophila Proteins/genetics*
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster/genetics
  • Drosophila melanogaster/growth & development
  • Eye/growth & development
  • Eye/metabolism*
  • Hedgehog Proteins/genetics
  • Kinesin/genetics*
  • Kinesin/metabolism
  • Mice
  • Photoreceptor Cells/metabolism
  • Polyubiquitin
  • Proteolysis
  • RNA, Small Interfering
  • Signal Transduction
  • Ubiquitin-Protein Ligases/genetics*
  • Ubiquitin-Protein Ligases/metabolism
  • Ubiquitination
  • Zebrafish/genetics
PubMed: 27195754 Full text @ PLoS Genet.
Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require Hh signaling are affected in zebrafish. Mouse UBR3 poly-ubiquitinates Kif7, the mammalian homologue of Cos2. Finally, loss of UBR3 up-regulates Kif7 protein levels and decreases Hh signaling in cultured cells. In summary, our work identifies Ubr3 as a novel, evolutionarily conserved modulator of Hh signaling that boosts Hh in some tissues.