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Li, T., Fan, J., Blanco-S├ínchez, 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. (2016). Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination.  PLoS Genet. 12(5): e1006054.
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Research paper

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.

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PubMed Central ID
PMC4873228 (PMC) (EuropePMC)
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Personal communication to FlyBase

P{UAS-cos.H} and PBac{Ubr3.18.3} insertions.
Bellen, 2017.1.20, P{UAS-cos.H} and PBac{Ubr3.18.3} insertions. [FBrf0234645]

Ubr3 constructs and insertions.
Bellen, 2017.1.20, Ubr3 constructs and insertions. [FBrf0234794]

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    Publication Type
    PLoS Genet.
    PLoS Genetics
    Publication Year
    1553-7404 1553-7390
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