Cullin 3 targets the tumor suppressor gene ARMC5 for ubiquitination and degradation
| Autor: | Anna Vaczlavik, Eric Clauser, Isadora Pontes Cavalcante, Maria Candida Barisson Villares Fragoso, Jérôme Bertherat, Ludivine Drougat, Marthe Rizk-Rabin, Claudimara Ferini Pacicco Lotfi, Christopher Ribes, Bruno Ragazzon, Karine Perlemoine |
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| Přispěvatelé: | Université de Paris, Institut Cochin, Institut National de la Santé et de la Recherche Médicale INSERM U1016, Centre National de la Recherche Scientifique CNRS UMR8104, F-75014 Paris. |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Cyclin E Tumor suppressor gene [SDV]Life Sciences [q-bio] Endocrinology Diabetes and Metabolism Mutant Transfection 03 medical and health sciences 0302 clinical medicine Endocrinology Ubiquitin Humans ComputingMilieux_MISCELLANEOUS Armadillo Domain Proteins biology Ubiquitination Cell cycle REGULAÇÃO NEOPLÁSICA DA EXPRESSÃO GÊNICA Cullin Proteins Cell biology 030104 developmental biology Oncology Proteasome 030220 oncology & carcinogenesis Armadillo repeats biology.protein Cullin |
| Zdroj: | Endocrine-Related Cancer Endocrine-Related Cancer, BioScientifica, 2020, 27 (4), pp.221-230. ⟨10.1530/ERC-19-0502⟩ Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1479-6821 1351-0088 |
| Popis: | ARMC5 (Armadillo repeat containing 5 gene) was identified as a new tumor suppressor gene responsible for hereditary adrenocortical tumors and meningiomas. ARMC5 is ubiquitously expressed and encodes a protein which contains a N-terminal Armadillo repeat domain and a C-terminal BTB (Bric-a-Brac, Tramtrack and Broad-complex) domain, both docking platforms for numerous proteins. At present, expression regulation and mechanisms of action of ARMC5 are almost unknown. In this study, we showed that ARMC5 interacts with CUL3 requiring its BTB domain. This interaction leads to ARMC5 ubiquitination and further degradation by the proteasome. ARMC5 alters cell cycle (G1/S phases and cyclin E accumulation) and this effect is blocked by CUL3. Moreover, missense mutants in the BTB domain of ARMC5, identified in patients with multiple adrenocortical tumors, are neither able to interact and be degraded by CUL3/proteasome nor alter cell cycle. These data show a new mechanism of regulation of the ARMC5 protein and open new perspectives in the understanding of its tumor suppressor activity. |
| Databáze: | OpenAIRE |
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