PXD042098

PXD042098 is an original dataset announced via ProteomeXchange.

Title	Deciphering TRIM69 interactors and its phosphor-proteomic regulation in centrosome dynamics
Description	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. To identify potential effectors of TRIM69 in regulating centrosome dynamics, we performed mass-spectrometry analysis of immunopurified TRIM69 complexes and defined the TRIM69 protein-interaction network. We discovered Serine/threonine-protein kinase 3 (MST2) as a new direct binding partner of TRIM69 and TRIM69 redistributes MST2 to the perinuclear cytoskeleton. Additionally, we performed IP mass- spectrometry analysis to define the MST2 interactome in the presence and absence of co-expressed TRIM69A. We found that WT TRIM69A (but not the E3 ligase mutant) promoted complex formation between MST2 and PLK1 in the detergent-insoluble CSK compartment. PLK1-mediated phosphorylation of MST2 at S15, S18 and S316 is crucial for centrosome disjunction. Analysis of MST2 phospho-peptides from the LC-MS/MS experiment revealed increased phosphorylation of S15, S316 and several other residues in the detergent-insoluble fraction of TRIM69A-overexpressing cells. Our findings suggest that TRIM69 is a new proximal regulator of distinct signaling pathways that regulate centrosome dynamics and promote bipolar mitosis. Further studies are necessary to identify the putative TRIM69A substrate(s) whose ubiquitination is necessary for regulating and interacting MST2 and centrosome dynamics. To address this issue, we have performed an unbiased mass spectrometry screen for TRIM69A-induced ubiquitination events.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:27:45.441.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine Mills
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-09 15:23:45	ID requested
1	2024-01-26 13:54:37	announced
⏵ 2	2024-10-22 06:27:46	announced	2024-10-22: Updated project metadata.

10.1093/nar/gkad766;

Wang Y, Risteski P, Yang Y, Chen H, Droby G, Walens A, Jayaprakash D, Troester M, Herring L, Chernoff J, Toli, ć IM, Bowser J, Vaziri C, The TRIM69-MST2 signaling axis regulates centrosome dynamics and chromosome segregation. Nucleic Acids Res, 51(19):10568-10589(2023) [pubmed]

submitter keyword: KGG,Centrosome dynamics, Phosphoproteomic profiling, IP mass-spectrometry

Cyrus Vaziri
contact affiliation	University of North Carolina Biochemistry and Biophysics; University of North Carolina Pathology and Laboratory Medicine; University of North Carolina Genetics and Molecular Biology Curriculum; University of North Carolina Lineberger Comprehensive Cancer Center.
contact email	cyrus_vaziri@med.unc.edu
lab head
Christine Mills
contact affiliation	University of North Carolina - Chapel Hill
contact email	allie.mills@unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042098
     1. Label: PRIDE project
     2. Name: Deciphering TRIM69 interactors and its phosphor-proteomic regulation in centrosome dynamics