Balestra, Fernando R.Domínguez-Calvo, AndrésWolf, BenitaBusso, CoralieBuff, AlizéeAverink, TessaLipsanen-Nyman, MaritaHuertas, PabloRíos, Rosa M.Gönczy, Pierre2022-09-022022-09-022021-06-25Balestra FR, Domínguez-Calvo A, Wolf B, Busso C, Buff A, Averink T, et al. TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin. Elife. 2021 Jan 25;10:e62640http://hdl.handle.net/10668/3984TRIM37 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/CellsMulibrey nanismE3 ubiquitin ligaseCentriolesEnzymesCélulasEnanismo mulibreyUbiquitina-proteína ligasasCentriolosEnzimasMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell CycleMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell LineageMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Microtubule-Organizing Center::Centrosome::CentriolesMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::HeLa CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Cytoskeleton::Microtubule-Organizing CenterMedical Subject Headings::Diseases::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Dwarfism::Mulibrey NanismMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Ligases::Ubiquitin-Protein Ligase Complexes::Ubiquitin-Protein Ligasesresearch article33491649Acceso abierto10.7554/eLife.626402050-084XPMC7870141