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| 001 | 126086 | ||
| 005 | 20240228135023.0 | ||
| 024 | 7 | _ | |a 10.1073/pnas.1322362111 |2 doi |
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| 024 | 7 | _ | |a 1091-6490 |2 ISSN |
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| 041 | _ | _ | |a eng |
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| 100 | 1 | _ | |a Rack, Paul G |b 0 |
| 245 | _ | _ | |a Arhgap36-dependent activation of Gli transcription factors. |
| 260 | _ | _ | |a Washington, DC |c 2014 |b National Acad. of Sciences |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1505392518_24934 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Hedgehog (Hh) pathway activation and Gli-dependent transcription play critical roles in embryonic patterning, tissue homeostasis, and tumorigenesis. By conducting a genome-scale cDNA overexpression screen, we have identified the Rho GAP family member Arhgap36 as a positive regulator of the Hh pathway in vitro and in vivo. Arhgap36 acts in a Smoothened (Smo)-independent manner to inhibit Gli repressor formation and to promote the activation of full-length Gli proteins. Arhgap36 concurrently induces the accumulation of Gli proteins in the primary cilium, and its ability to induce Gli-dependent transcription requires kinesin family member 3a and intraflagellar transport protein 88, proteins that are essential for ciliogenesis. Arhgap36 also functionally and biochemically interacts with Suppressor of Fused. Transcriptional profiling further reveals that Arhgap36 is overexpressed in murine medulloblastomas that acquire resistance to chemical Smo inhibitors and that ARHGAP36 isoforms capable of Gli activation are up-regulated in a subset of human medulloblastomas. Our findings reveal a new mechanism of Gli transcription factor activation and implicate ARHGAP36 dysregulation in the onset and/or progression of GLI-dependent cancers. |
| 536 | _ | _ | |a 312 - Functional and structural genomics (POF3-312) |0 G:(DE-HGF)POF3-312 |c POF3-312 |f POF III |x 0 |
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| 650 | _ | 7 | |a GLI1 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a GTPase-Activating Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Gli protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Hedgehog Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Kruppel-Like Transcription Factors |2 NLM Chemicals |
| 650 | _ | 7 | |a Nuclear Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Receptors, G-Protein-Coupled |2 NLM Chemicals |
| 650 | _ | 7 | |a SMO protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Smo protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Smoothened Receptor |2 NLM Chemicals |
| 650 | _ | 7 | |a Transcription Factors |2 NLM Chemicals |
| 650 | _ | 7 | |a Zebrafish Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Zinc Finger Protein GLI1 |2 NLM Chemicals |
| 700 | 1 | _ | |a Ni, Jun |b 1 |
| 700 | 1 | _ | |a Payumo, Alexander Y |b 2 |
| 700 | 1 | _ | |a Nguyen, Vien |b 3 |
| 700 | 1 | _ | |a Crapster, J Aaron |b 4 |
| 700 | 1 | _ | |a Hovestadt, Volker |0 P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc |b 5 |u dkfz |
| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 6 |u dkfz |
| 700 | 1 | _ | |a Jones, David |0 P:(DE-He78)551bb92841f634070997aa168d818492 |b 7 |u dkfz |
| 700 | 1 | _ | |a Mich, John K |b 8 |
| 700 | 1 | _ | |a Firestone, Ari J |b 9 |
| 700 | 1 | _ | |a Pfister, Stefan |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 10 |u dkfz |
| 700 | 1 | _ | |a Cho, Yoon-Jae |b 11 |
| 700 | 1 | _ | |a Chen, James K |b 12 |
| 773 | _ | _ | |a 10.1073/pnas.1322362111 |g Vol. 111, no. 30, p. 11061 - 11066 |0 PERI:(DE-600)1461794-8 |n 30 |p 11061 - 11066 |t Proceedings of the National Academy of Sciences of the United States of America |v 111 |y 2014 |x 1091-6490 |
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