TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin
| Autor: | Pablo Huertas, Fernando R. Balestra, Benita Wolf, Marita Lipsanen-Nyman, Rosa M. Ríos, Alizée Buff, Pierre Gönczy, Coralie Busso, Tessa Averink, Andrés Domínguez-Calvo |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Genética, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, University of Helsinki, Helsinki University Hospital Area, [Balestra,FR, Domínguez-Calvo,A, Huertas,P] Departamento de Genética, Universidad de Sevilla, Sevilla, Spain. [Balestra,FR, Huertas,P, Ríos,RM] Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC-Universidad Pablo de Olavide, Sevilla, Spain. [Wolf,B, Busso,C, Buff,A, Averink,T, Gönczy,P] Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland. [Lipsanen-Nyman,M] Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Swiss Cancer Research foundation KLS-3388-02-2014 Pierre Gönczy, European Research Council Marie Curie Intra-European Fellowships PIEF-GA-2013-629414 Fernando R Balestra Rosa M Ríos, Swiss National Science Foundation Alizée Buff, University of Seville postdoctoral contract of the V PPIT-US Fernando R Balestra Junta de Andalucía CABIMER Fernando R Balestra |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mulibrey nanism COILED-COIL PROTEIN MICROTUBULE NUCLEATION Centriole Enzimas microtubule organizing center MULIBREY NANISM Cell Cycle Proteins POLO KINASE DE-NOVO Tripartite Motif Proteins Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] 0302 clinical medicine 3123 Gynaecology and paediatrics cell biology Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Microtubule-Organizing Center [Medical Subject Headings] Biology (General) Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle [Medical Subject Headings] Enanismo mulibrey Centrioles Diseases::Congenital Hereditary and Neonatal Diseases and Abnormalities::Genetic Diseases Inborn::Dwarfism::Mulibrey Nanism [Medical Subject Headings] biology Chemistry General Neuroscience General Medicine CLEM Ubiquitin ligase Cell biology Enzymes SINGLE PROCENTRIOLE E3 ubiquitin ligase Medicine PLK4 Research Article Human centrobin QH301-705.5 Science TRIM37 E3 ligase Ubiquitin-Protein Ligases Cells Centriolos 3122 Cancers General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Ubiquitina-proteína ligasas Células medicine Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Ligases::Ubiquitin-Protein Ligase Complexes::Ubiquitin-Protein Ligases [Medical Subject Headings] Humans CENTROSOME human Microtubule nucleation General Immunology and Microbiology DAUGHTER CENTRIOLES Microtubule organizing center Cell Biology medicine.disease Phenomena and Processes::Cell Physiological Phenomena::Cell Lineage [Medical Subject Headings] Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Microtubule-Organizing Center::Centrosome::Centrioles [Medical Subject Headings] 030104 developmental biology Centrosome Centrin CELLS biology.protein Anatomy::Cells::Cells Cultured::Cell Line::Cell Line Tumor::HeLa Cells [Medical Subject Headings] 030217 neurology & neurosurgery Microtubule-Organizing Center HeLa Cells |
| Zdroj: | idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) idUS. Depósito de Investigación de la Universidad de Sevilla instname eLife eLife, Vol 10 (2021) |
| Popis: | TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in supernumerary foci bearing the centriolar protein Centrin. Here, we characterize these centriolar protein assemblies (Cenpas) to uncover the mechanism of action of TRIM37. We find that an atypical de novo assembly pathway can generate Cenpas that act as microtubule organizing centers (MTOCs), including in Mulibrey patient cells. Correlative light electron microscopy reveals that Cenpas are centriole-related or electron-dense structures with stripes. TRIM37 regulates the stability and solubility of Centrobin, which accumulates in elongated entities resembling the striped electron dense structures upon TRIM37 depletion. Furthermore, Cenpas formation upon TRIM37 depletion requires PLK4, as well as two parallel pathways relying respectively on Centrobin and PLK1. Overall, our work uncovers how TRIM37 prevents Cenpas formation, which would otherwise threaten genome integrity, including in Mulibrey patients. |
| Databáze: | OpenAIRE |
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