Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. (Articolo in rivista)

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  • Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1038/ncb2013 (literal)
Alternative label
  • Canettieri G; Di Marcotullio L; Greco A; Coni S; Antonucci L; Infante P; Pietrosanti L; De Smaele E; Ferretti E; Miele E; Pelloni M; De Simone G; Pedone EM; Gallinari P; Giorgi A; Steinkühler C; Vitagliano L; Pedone C; Schinin ME; Screpanti I; Gulino A. (2010)
    Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation.
    in Nature cell biology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Canettieri G; Di Marcotullio L; Greco A; Coni S; Antonucci L; Infante P; Pietrosanti L; De Smaele E; Ferretti E; Miele E; Pelloni M; De Simone G; Pedone EM; Gallinari P; Giorgi A; Steinkühler C; Vitagliano L; Pedone C; Schinin ME; Screpanti I; Gulino A. (literal)
Pagina inizio
  • 132 (literal)
Pagina fine
  • 142 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 12 (literal)
Rivista
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Experimental Medicine, Sapienza University, 324 viale Regina Elena, 00161 Rome, Italy; Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Naples, Italy; Istituto di Ricerche di Biologia Molecolare P. Angeletti-IRBM-Merck Research Laboratories Rome, Pomezia, Italy; Departement of Biochemical Science \"Sapienza\" University of Rome, Italy; (literal)
Titolo
  • Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. (literal)
Abstract
  • Hedgehog signalling is crucial for development and is deregulated in several tumours, including medulloblastoma. Regulation of the transcriptional activity of Gli (glioma-associated oncogene) proteins, effectors of the Hedgehog pathway, is poorly understood. We show here that Gli1 and Gli2 are acetylated proteins and that their HDAC-mediated deacetylation promotes transcriptional activation and sustains a positive autoregulatory loop through Hedgehog-induced upregulation of HDAC1. This mechanism is turned off by HDAC1 degradation through an E3 ubiquitin ligase complex formed by Cullin3 and REN, a Gli antagonist lost in human medulloblastoma. Whereas high HDAC1 and low REN expression in neural progenitors and medulloblastomas correlates with active Hedgehog signalling, loss of HDAC activity suppresses Hedgehog-dependent growth of neural progenitors and tumour cells. Consistent with this, abrogation of Gli1 acetylation enhances cellular proliferation and transformation. These data identify an integrated HDAC- and ubiquitin-mediated circuitry, where acetylation of Gli proteins functions as an unexpected key transcriptional checkpoint of Hedgehog signalling (literal)
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