000126086 001__ 126086 000126086 005__ 20240228135023.0 000126086 0247_ $$2doi$$a10.1073/pnas.1322362111 000126086 0247_ $$2pmid$$apmid:25024229 000126086 0247_ $$2pmc$$apmc:PMC4121843 000126086 0247_ $$2ISSN$$a0027-8424 000126086 0247_ $$2ISSN$$a1091-6490 000126086 0247_ $$2altmetric$$aaltmetric:2562350 000126086 037__ $$aDKFZ-2017-02201 000126086 041__ $$aeng 000126086 082__ $$a000 000126086 1001_ $$aRack, Paul G$$b0 000126086 245__ $$aArhgap36-dependent activation of Gli transcription factors. 000126086 260__ $$aWashington, DC$$bNational Acad. of Sciences$$c2014 000126086 3367_ $$2DRIVER$$aarticle 000126086 3367_ $$2DataCite$$aOutput Types/Journal article 000126086 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1505392518_24934 000126086 3367_ $$2BibTeX$$aARTICLE 000126086 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000126086 3367_ $$00$$2EndNote$$aJournal Article 000126086 520__ $$aHedgehog (Hh) pathway activation and Gli-dependent transcription play critical roles in embryonic patterning, tissue homeostasis, and tumorigenesis. By conducting a genome-scale cDNA overexpression screen, we have identified the Rho GAP family member Arhgap36 as a positive regulator of the Hh pathway in vitro and in vivo. Arhgap36 acts in a Smoothened (Smo)-independent manner to inhibit Gli repressor formation and to promote the activation of full-length Gli proteins. Arhgap36 concurrently induces the accumulation of Gli proteins in the primary cilium, and its ability to induce Gli-dependent transcription requires kinesin family member 3a and intraflagellar transport protein 88, proteins that are essential for ciliogenesis. Arhgap36 also functionally and biochemically interacts with Suppressor of Fused. Transcriptional profiling further reveals that Arhgap36 is overexpressed in murine medulloblastomas that acquire resistance to chemical Smo inhibitors and that ARHGAP36 isoforms capable of Gli activation are up-regulated in a subset of human medulloblastomas. Our findings reveal a new mechanism of Gli transcription factor activation and implicate ARHGAP36 dysregulation in the onset and/or progression of GLI-dependent cancers. 000126086 536__ $$0G:(DE-HGF)POF3-312$$a312 - Functional and structural genomics (POF3-312)$$cPOF3-312$$fPOF III$$x0 000126086 588__ $$aDataset connected to CrossRef, PubMed, 000126086 650_7 $$2NLM Chemicals$$aGLI1 protein, human 000126086 650_7 $$2NLM Chemicals$$aGTPase-Activating Proteins 000126086 650_7 $$2NLM Chemicals$$aGli protein, mouse 000126086 650_7 $$2NLM Chemicals$$aHedgehog Proteins 000126086 650_7 $$2NLM Chemicals$$aKruppel-Like Transcription Factors 000126086 650_7 $$2NLM Chemicals$$aNuclear Proteins 000126086 650_7 $$2NLM Chemicals$$aReceptors, G-Protein-Coupled 000126086 650_7 $$2NLM Chemicals$$aSMO protein, human 000126086 650_7 $$2NLM Chemicals$$aSmo protein, mouse 000126086 650_7 $$2NLM Chemicals$$aSmoothened Receptor 000126086 650_7 $$2NLM Chemicals$$aTranscription Factors 000126086 650_7 $$2NLM Chemicals$$aZebrafish Proteins 000126086 650_7 $$2NLM Chemicals$$aZinc Finger Protein GLI1 000126086 7001_ $$aNi, Jun$$b1 000126086 7001_ $$aPayumo, Alexander Y$$b2 000126086 7001_ $$aNguyen, Vien$$b3 000126086 7001_ $$aCrapster, J Aaron$$b4 000126086 7001_ $$0P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aHovestadt, Volker$$b5$$udkfz 000126086 7001_ $$0P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aKool, Marcel$$b6$$udkfz 000126086 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b7$$udkfz 000126086 7001_ $$aMich, John K$$b8 000126086 7001_ $$aFirestone, Ari J$$b9 000126086 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b10$$udkfz 000126086 7001_ $$aCho, Yoon-Jae$$b11 000126086 7001_ $$aChen, James K$$b12 000126086 773__ $$0PERI:(DE-600)1461794-8$$a10.1073/pnas.1322362111$$gVol. 111, no. 30, p. 11061 - 11066$$n30$$p11061 - 11066$$tProceedings of the National Academy of Sciences of the United States of America$$v111$$x1091-6490$$y2014 000126086 909CO $$ooai:inrepo02.dkfz.de:126086$$pVDB 000126086 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)744146d3b5a3df1e0ac555e5bf1ee5cc$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ 000126086 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ 000126086 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)551bb92841f634070997aa168d818492$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ 000126086 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ 000126086 9131_ $$0G:(DE-HGF)POF3-312$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunctional and structural genomics$$x0 000126086 9141_ $$y2014 000126086 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium 000126086 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000126086 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000126086 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000126086 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bP NATL ACAD SCI USA : 2015 000126086 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search 000126086 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC 000126086 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List 000126086 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000126086 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000126086 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000126086 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences 000126086 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000126086 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record 000126086 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000126086 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bP NATL ACAD SCI USA : 2015 000126086 9201_ $$0I:(DE-He78)B060-20160331$$kB060$$lMolekulare Genetik$$x0 000126086 9201_ $$0I:(DE-He78)B062-20160331$$kB062$$lPädiatrische Neuroonkologie$$x1 000126086 980__ $$ajournal 000126086 980__ $$aVDB 000126086 980__ $$aI:(DE-He78)B060-20160331 000126086 980__ $$aI:(DE-He78)B062-20160331 000126086 980__ $$aUNRESTRICTED