Ubr3, a Novel Modulator of Hh Signaling Affects the Degradation of Costal-2 and Kif7 through Poly-ubiquitination
Year: 2016
Type: article
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.
Source: PLoS Genetics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Defense, Howard Hughes Medical Institute, Friedreich's Ataxia Research Alliance, Baylor College of Medicine, Robert A. and Renee E. Belfer Family Foundation, Target ALS, Huffington Foundation, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: The Regulation of Smoothened in Hedgehog Signaling, G2087349970, Signaling Hierarchies in Vertebrate Development, Baylor Intellectual and Developmental Disabilities Research Centers, Mapping and rescuing EMS-induced lethal mutations on the Drosophila X Chromosome, G4060687680, Genetic Regulation of Inner Ear Formation, G5465708471, Center for Systematic Modeling of Cancer Development, G5741446764, Using Drosophila to identify human deafness genes, G7618450163, STAT3 SIGNALING IN BREAST CANCER STEM CELL REGULATION, G8827130515, G9000048136, G9000066955, G9000229713, G9000240210, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2405103990