title: A BCL6/BCOR/SIRT1 complex triggers neurogenesis and suppresses medulloblastoma by repressing Sonic Hedgehog signaling.
abstract: Disrupted differentiation during development can lead to oncogenesis, but the underlying mechanisms remain poorly understood. Here we identify BCL6, a transcriptional repressor and lymphoma oncoprotein, as a pivotal factor required for neurogenesis and tumor suppression of medulloblastoma (MB). BCL6 is necessary for and capable of preventing the development of GNP-derived MB in mice, and can block the growth of human MB cells in vitro. BCL6 neurogenic and oncosuppressor effects rely on direct transcriptional repression of Gli1 and Gli2 effectors of the SHH pathway, through recruitment of BCOR corepressor and SIRT1 deacetylase. Our findings identify the BCL6/BCOR/SIRT1 complex as a potent repressor of the SHH pathway in normal and oncogenic neural development, with direct diagnostic and/or therapeutic relevance for SHH MB.
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Luca
authors.initials: L
authors.lastname: Tiberi
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bonnefont
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Jelle
authors.initials: J
authors.lastname: van den Ameele
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Serge-Daniel
authors.initials: SD
authors.lastname: Le Bon
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Adèle
authors.initials: A
authors.lastname: Herpoel
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium.
authors.forename: Angéline
authors.initials: A
authors.lastname: Bilheu
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Beverly W
authors.initials: BW
authors.lastname: Baron
authors.affiliation: Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), and ULB Institute of Neuroscience (UNI), 808 Route de Lennik, 1070 Brussels, Belgium; Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium. Electronic address: pierre.vanderhaeghen@ulb.ac.be.
authors.forename: Pierre
authors.initials: P
authors.lastname: Vanderhaeghen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D015513:Oncogene Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: C084103:BCL6 protein, human; C411984:BCOR protein, human; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; D056564:Sirtuin 1