Please use this identifier to cite or link to this item: http://hdl.handle.net/10077/10119
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dc.contributor.advisorDel Sal, Gianninoit_IT
dc.contributor.authorSorrentino, Giovanniit_IT
dc.date.accessioned2014-07-08T11:34:42Z-
dc.date.available2014-07-08T11:34:42Z-
dc.date.issued2014-04-28it_IT
dc.identifier.urihttp://hdl.handle.net/10077/10119-
dc.description2012/2013it_IT
dc.description.abstractThe YAP and TAZ mediators of the Hippo pathway (hereafter called YAP/TAZ) promote tissue proliferation and organ growth. However, how their biological properties intersect with cellular metabolism remains unexplained. Here, we show that YAP/TAZ activity is controlled by the SREBP/mevalonate pathway. Inhibition of the rate-limiting enzyme of this pathway (HMG-CoA reductase) by statins opposes YAP/TAZ nuclear localization and transcriptional responses. Mechanistically, the geranylgeranyl pyrophosphate produced by the mevalonate cascade is required for activation of Rho GTPases that, in turn, activate YAP/TAZ by inhibiting their phosphorylation and promoting their nuclear accumulation. The mevalonate–YAP/TAZ axis is required for proliferation and self-renewal of breast cancer cells. In Drosophila melanogaster, inhibition of mevalonate biosynthesis and geranylgeranylation blunts the eye overgrowth induced by Yorkie, the YAP/TAZ orthologue. In tumour cells, YAP/TAZ activation is promoted by increased levels of mevalonic acid produced by SREBP transcriptional activity, which is induced by its oncogenic cofactor mutant p53. These findings reveal an additional layer of YAP/TAZ regulation by metabolic cues.it_IT
dc.language.isoenit_IT
dc.publisherUniversità degli studi di Triesteit_IT
dc.rights.urihttp://www.openstarts.units.it/dspace/default-license.jsp-
dc.subjectCancerit_IT
dc.subjectSmall moleculesit_IT
dc.subjectHippo pathwayit_IT
dc.subjectMetabolismit_IT
dc.subjectp53it_IT
dc.subject.classificationSCUOLA DI DOTTORATO DI RICERCA IN BIOMEDICINA MOLECOLAREit_IT
dc.titleMetabolic control of YAP/TAZ by the Mevalonate Pathwayit_IT
dc.typeDoctoral Thesis-
dc.subject.miurBIO/13 BIOLOGIA APPLICATAit_IT
dc.description.cycleXXVI Cicloit_IT
dc.rights.statementNO EMBARGOit_IT
dc.identifier.nbnurn:nbn:it:units-12541-
dc.description.birth1983-
item.grantfulltextopen-
item.languageiso639-1other-
item.fulltextWith Fulltext-
Appears in Collections:Scienze biologiche
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