| http://purl.uniprot.org/citations/21472142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21472142 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21472142 | http://www.w3.org/2000/01/rdf-schema#comment | "Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh) signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent a potential therapeutic target for Hh-dependent tumors, but still little information is available on the physiological mechanisms of HDAC regulation. The putative tumor suppressor REN(KCTD11) acts through ubiquitination-dependent degradation of HDAC1, thereby affecting Hh activity and medulloblastoma growth. We identify and characterize here two REN(KCTD11) homologues, defining a new family of proteins named KCASH, as "KCTD containing, Cullin3 adaptor, suppressor of Hedgehog." Indeed, the novel genes (KCASH2(KCTD21) and KCASH3(KCTD6)) share with REN(KCTD11) a number of features, such as a BTB domain required for the formation of a Cullin3 ubiquitin ligase complex and HDAC1 ubiquitination and degradation capability, suppressing the acetylation-dependent Hh/Gli signaling. Expression of KCASH2 and -3 is observed in cerebellum, whereas epigenetic silencing and allelic deletion are observed in human medulloblastoma. Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis. Accordingly, they might represent a promising class of endogenous "agents" through which this pathway may be targeted."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.org/dc/terms/identifier | "doi:10.1593/neo.101630"xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.org/dc/terms/identifier | "doi:10.1593/neo.101630"xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Canettieri G."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Canettieri G."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Greco A."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Greco A."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Bei R."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Bei R."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Screpanti I."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Screpanti I."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Di Marcotullio L."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Di Marcotullio L."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Coni S."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Coni S."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Gulino A."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Gulino A."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Infante P."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Infante P."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "De Smaele E."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "De Smaele E."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Ferretti E."xsd:string |
| http://purl.uniprot.org/citations/21472142 | http://purl.uniprot.org/core/author | "Ferretti E."xsd:string |