TRIM37 prevents formation of centriolar protein assemblies by regulating Centrobin.

Abstract

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.

• Authors: Fernando R Balestra, Andrés Domínguez-Calvo, Benita Wolf, Coralie Busso, Alizée Buff, Tessa Averink, Marita Lipsanen-Nyman, Pablo Huertas, Rosa M Ríos, Pierre Gönczy
• Journal: eLife (Elife) Vol. 10 (01 25 2021) ISSN: 2050-084X [Electronic] England
• PMID: 33491649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021, Balestra et al.

Chemical References

• CNTROB protein, human
• Cell Cycle Proteins
• Tripartite Motif Proteins
• TRIM37 protein, human
• Ubiquitin-Protein Ligases

Topics

• Cell Cycle Proteins (genetics, metabolism)
• Cell Line
• Centrioles (metabolism)
• HeLa Cells
• Humans
• Microtubule-Organizing Center (metabolism)
• Mulibrey Nanism (genetics, metabolism)
• Tripartite Motif Proteins (genetics, metabolism)
• Ubiquitin-Protein Ligases (genetics, metabolism)