The TRIM69-MST2 signaling axis regulates centrosome dynamics and chromosome segregation

Yilin Wang, Patrik Risteski, Yang Yang, Huan Chen, Gaith Droby, Andrea Walens, Deepika Jayaprakash, Melissa A. Troester, Laura Herring, Jonathan Chernoff, Iva M. Tolić, Jessica Bowser, Cyrus Vaziri

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Stringent control of centrosome duplication and separation is important for preventing chromosome instability. Structural and numerical alterations in centrosomes are hallmarks of neoplastic cells and contribute to tumorigenesis. We show that a Centrosome Amplification 20 (CA20) gene signature is associated with high expression of the Tripartite Motif (TRIM) family member E3 ubiquitin ligase, TRIM69. TRIM69-ablation in cancer cells leads to centrosome scattering and chromosome segregation defects. We identify Serine/threonine-protein kinase 3 (MST2) as a new direct binding partner of TRIM69. TRIM69 redistributes MST2 to the perinuclear cytoskeleton, promotes its association with Polo-like kinase 1 (PLK1) and stimulates MST2 phosphorylation at S15 (a known PLK1 phosphorylation site that is critical for centrosome disjunction). TRIM69 also promotes microtubule bundling and centrosome segregation that requires PRC1 and DYNEIN. Taken together, we identify TRIM69 as a new proximal regulator of distinct signaling pathways that regulate centrosome dynamics and promote bipolar mitosis.

Original languageEnglish
Pages (from-to)10568-10589
Number of pages22
JournalNucleic Acids Research
Volume51
Issue number19
DOIs
StatePublished - Oct 27 2023

Keywords

  • Cell Cycle Proteins/metabolism
  • Centrosome/metabolism
  • Chromosome Segregation
  • Mitosis/genetics
  • Phosphorylation
  • Signal Transduction
  • Spindle Apparatus/metabolism

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