TY - JOUR TI - TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin AU - Balestra, Fernando R AU - Domínguez-Calvo, Andrés AU - Wolf, Benita AU - Busso, Coralie AU - Buff, Alizée AU - Averink, Tessa AU - Lipsanen-Nyman, Marita AU - Huertas, Pablo AU - Ríos, Rosa M AU - Gönczy, Pierre A2 - Lüders, Jens A2 - Sengupta, Piali VL - 10 PY - 2021 DA - 2021/01/25 SP - e62640 C1 - eLife 2021;10:e62640 DO - 10.7554/eLife.62640 UR - https://doi.org/10.7554/eLife.62640 AB - 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. KW - TRIM37 E3 ligase KW - Mulibrey nanism KW - Centriole KW - microtubule organizing center KW - centrobin KW - CLEM JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -