ArticlePloS one2011
In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
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- Histamine synthesis and transport are coupled in axon terminals via a dual quality control system.The EMBO journal · 2024Article
- The E3 ligase Thin controls homeostatic plasticity through neurotransmitter release repression.eLife · 2022Article
- Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.Genes to cells : devoted to molecular & cellular mechanisms · 2022Review
- Genetic mapping ofmicroPublication biology · 2022Article
- SCF-Fbxo42 promotes synaptonemal complex assembly by downregulating PP2A-B56.The Journal of cell biology · 2021Article
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- A screen for E3 ubiquitination ligases that genetically interact with the adaptor protein Cindr during Drosophila eye patterning.PloS one · 2017Article
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- Stuxnet Facilitates the Degradation of Polycomb Protein during Development.Developmental cell · 2016Article
- Smoothened regulation in response to Hedgehog stimulation.Frontiers in biology · 2015Article
- The wavy Mutation Maps to the Inositol 1,4,5-Trisphosphate 3-Kinase 2 (IP3K2) Gene of Drosophila and Interacts with IP3R to Affect Wing Development.G3 (Bethesda, Md.) · 2015Article
- In vivo shRNA screens in solid tumors.Nature protocols · 2014Article
- Ubpy controls the stability of the ESCRT-0 subunit Hrs in development.Development (Cambridge, England) · 2014Article
- Article
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- A targeted in vivo RNAi screen reveals deubiquitinases as new regulators of Notch signaling.G3 (Bethesda, Md.) · 2012Article
- Modification by ubiquitin-like proteins: significance in apoptosis and autophagy pathways.International journal of molecular sciences · 2012Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Hedgehog (Hh) signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi) screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub) and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12) that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci), the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.