| http://purl.uniprot.org/citations/29127155 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29127155 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29127155 | http://www.w3.org/2000/01/rdf-schema#comment | "The tumor suppressors Tsc1 and Tsc2 form the tuberous sclerosis complex (TSC), a regulator of mTOR activity. Tsc1 stabilizes Tsc2; however, the precise mechanism involved remains elusive. The molecular chaperone heat-shock protein 90 (Hsp90) is an essential component of the cellular homeostatic machinery in eukaryotes. Here, we show that Tsc1 is a new co-chaperone for Hsp90 that inhibits its ATPase activity. The C-terminal domain of Tsc1 (998-1,164 aa) forms a homodimer and binds to both protomers of the Hsp90 middle domain. This ensures inhibition of both subunits of the Hsp90 dimer and prevents the activating co-chaperone Aha1 from binding the middle domain of Hsp90. Conversely, phosphorylation of Aha1-Y223 increases its affinity for Hsp90 and displaces Tsc1, thereby providing a mechanism for equilibrium between binding of these two co-chaperones to Hsp90. Our findings establish an active role for Tsc1 as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients-including Tsc2-thereby preventing their ubiquitination and proteasomal degradation."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.org/dc/terms/identifier | "doi:10.15252/embj.201796700"xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.org/dc/terms/identifier | "doi:10.15252/embj.201796700"xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Dunn D.M."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Dunn D.M."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Prodromou C."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Prodromou C."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Mollapour M."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Mollapour M."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Panaretou B."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Panaretou B."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Wong M."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Wong M."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Gutmann D.H."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Gutmann D.H."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Blanden A.R."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Blanden A.R."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Bourboulia D."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Bourboulia D."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Bratslavsky G."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Bratslavsky G."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Loh S.N."xsd:string |
| http://purl.uniprot.org/citations/29127155 | http://purl.uniprot.org/core/author | "Loh S.N."xsd:string |