FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells
| Autor: | Habel, Nadia, El-Hachem, Najla, Soysouvanh, Frédéric, Hadhiri-Bzioueche, Hanene, Giuliano, Serena, Nguyen, Sophie, Horák, Pavel, Gay, Anne-Sophie, Debayle, Delphine, Nottet, Nicolas, Béranger, Guillaume, Paillerets, Brigitte Bressac-de, Bertolotto, Corine, Ballotti, Robert |
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| Přispěvatelé: | Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
SKP Cullin F-Box Protein Ligases Ubiquitination Mice Nude Muscle Proteins [SDV.CAN]Life Sciences [q-bio]/Cancer Oncogenes Cellular Reprogramming Transfection Xenograft Model Antitumor Assays Article Epigenesis Genetic Mice [SDV.CAN] Life Sciences [q-bio]/Cancer Cell Line Tumor Animals Humans Epigenetics Melanoma Cell Proliferation |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, Nature Publishing Group, 2020, Online ahead of print. ⟨10.1038/s41418-020-00710-x⟩ Cell Death and Differentiation, 2020, Online ahead of print. ⟨10.1038/s41418-020-00710-x⟩ |
| ISSN: | 1350-9047 1476-5403 |
| DOI: | 10.1038/s41418-020-00710-x⟩ |
| Popis: | International audience; Ubiquitination by serving as a major degradation signal of proteins, but also by controlling protein functioning and localization, plays critical roles in most key cellular processes. Here, we show that MITF, the master transcription factor in melanocytes, controls ubiquitination in melanoma cells. We identified FBXO32, a component of the SCF E3 ligase complex as a new MITF target gene. FBXO32 favors melanoma cell migration, proliferation, and tumor development in vivo. Transcriptomic analysis shows that FBXO32 knockdown induces a global change in melanoma gene expression profile. These include the inhibition of CDK6 in agreement with an inhibition of cell proliferation and invasion upon FBXO32 silencing. Furthermore, proteomic analysis identifies SMARC4, a component of the chromatin remodeling complexes BAF/PBAF, as a FBXO32 partner. FBXO32 and SMARCA4 co-localize at loci regulated by FBXO32, such as CDK6 suggesting that FBXO32 controls transcription through the regulation of chromatin remodeling complex activity. FBXO32 and SMARCA4 are the components of a molecular cascade, linking MITF to epigenetics, in melanoma cells. |
| Databáze: | OpenAIRE |
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