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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.
FlyBase ID
FBrf0232422
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC4873228 (PMC) (EuropePMC)
Related Publication(s)
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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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Genet.
    Title
    PLoS Genetics
    Publication Year
    2005-
    ISBN/ISSN
    1553-7404 1553-7390
    Data From Reference