The TRIM69-MST2 signaling axis regulates centrosome dynamics and chromosome segregation.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
27 10 2023
27 10 2023
Historique:
accepted:
10
09
2023
revised:
30
08
2023
received:
10
05
2023
medline:
30
10
2023
pubmed:
23
9
2023
entrez:
22
9
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37739411
pii: 7280551
doi: 10.1093/nar/gkad766
pmc: PMC10602929
doi:
Substances chimiques
Cell Cycle Proteins
0
STK3 protein, human
EC 2.7.11.1
TRIM69 protein, human
EC 2.3.2.27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10568-10589Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM135128
Pays : United States
Organisme : NIH HHS
ID : S10 OD030223
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA229530
Pays : United States
Organisme : NIH HHS
ID : R01 ES009558
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES031007
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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