ArticleJournal of cell science2014
A central region of Gli2 regulates its localization to the primary cilium and transcriptional activity.
Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
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- Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking.Science advances · 2025Article
- Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.Science advances · 2025Article
- mTORC1 hampers Hedgehog signaling inLife science alliance · 2024Article
- MI-181 Modulates Cilia Length and Restores Cilia Length in Cells with Defective Shortened Cilia.ACS chemical biology · 2024Article
- Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development.Science advances · 2024Article
- The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium.Communications biology · 2024Article
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- Paralog-specific TTC30 regulation of Sonic hedgehog signaling.Frontiers in molecular biosciences · 2023Article
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- SANA: cross-species prediction of Gene Ontology GO annotations via topological network alignment.NPJ systems biology and applications · 2022Article
- A kinesin mimics DNA.Nature cell biology · 2022Article
- The Intimate Connection Between Lipids and Hedgehog Signaling.Frontiers in cell and developmental biology · 2022Review
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- Rabl2 GTP hydrolysis licenses BBSome-mediated export to fine-tune ciliary signaling.The EMBO journal · 2021Article
- Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling.American journal of human genetics · 2020Article
- NRF2-dependent gene expression promotes ciliogenesis and Hedgehog signaling.Scientific reports · 2019Article
- The deubiquitinating enzyme Usp14 controls ciliogenesis and Hedgehog signaling.Human molecular genetics · 2019Article
- Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Signaling through vertebrate Hedgehog (Hh) proteins depends on the primary cilium. In response to Hh signals, the transcriptional activator of the pathway, Gli2, accumulates at the ciliary tip, raising the possibility that ciliary localization is important for Gli2 activation. To test this hypothesis, we used the Floxin system to create knock-in Gli2 alleles in embryonic stem cells (ESCs) to allow methodical testing of which domains and residues are essential for the ciliary localization of Gli2. The Gli2 zinc fingers, transcriptional activation domain, repressor domain, phosphorylation cluster and a Sufu binding motif were each dispensable for ciliary localization. Mutating residues that are required for Gli2 sumoylation and nuclear trafficking also did not abrogate ciliary localization. By contrast, several other domains restricted Gli2 nuclear localization, and a central region, distinct from previously characterized domains, was required for ciliary localization. In addition to an inability to localize to cilia, Gli2 lacking this central domain was unable to activate target genes. Thus, our systematic analysis in ESCs reveals that distinct regions of Gli2 regulate its nuclear and ciliary localization. The identification of a domain essential for both ciliary localization and transcriptional activity suggests that ciliary localization of Gli2 is required for its activation.
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