PXD038990

PXD038990 is an original dataset announced via ProteomeXchange.

Title	Proteomics and phosphoproteomics analysis of SUM159 cells upon ClpP activation with ONC201 and TR57 compounds
Description	ClpP activators ONC201 and related small molecules (TR compounds, Madera Therapeutics), have demonstrated significant anti-cancer potential in an array of in vitro and in vivo studies, including clinical trials for refractory solid tumors. Though progress has been made in identifying specific phenotypic outcomes following ClpP activation, the exact mechanism by which ClpP activation leads to broad anti-cancer activity has yet to be fully elucidated. In this study, we utilized a multi-omics approach to identify the ClpP-dependent proteomic, transcriptomic, and metabolomic changes resulting from ONC201 or the TR compound TR-57 in triple-negative breast cancer cells. In this portion of the study, we applied mass spectrometry-based proteomics, and quantified ~8000 proteins. From the proteomics data, approximately 3400 (ONC201) and 3000 (TR-57) proteins increased and ~4600 (ONC201) and ~4800 (TR-57) proteins decreased. Gene ontology (GO) analysis revealed strong similarities between proteins up- or downregulated by ONC201 or TR-57 treatment. Notably, this included the downregulation of many mitochondrial processes and proteins, including mitochondrial translation and mitochondrial matrix proteins. Additionally, phosphoproteomics analysis was performed, quantifying ~17,000 phosphopetides, of which >800 were significantly upregulated and >1000 were significantly downregulated phosphopeptides across both ONC201 and TR-57 treatments. Between both treatments, 245 upregulated and 477 downregulated phosphopeptides were shared. Multiple kinases were predicted to be activated including ATM, ATR, AMPK and others, while other kinases were predicted to be inactivated including CDK2, CDK4 and AurB.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:47:28.823.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Herring
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-20 20:10:08	ID requested
1	2023-05-10 14:18:55	announced
⏵ 2	2023-11-14 08:47:29	announced	2023-11-14: Updated project metadata.

Fennell EMJ, Aponte-Collazo LJ, Pathmasiri W, Rushing BR, Barker NK, Partridge MC, Li YY, White CA, Greer YE, Herring LE, Lipkowitz S, Sumner SCJ, Iwanowicz EJ, Graves LM, Multi-omics analyses reveal ClpP activators disrupt essential mitochondrial pathways in triple-negative breast cancer. Front Pharmacol, 14():1136317(2023) [pubmed]

submitter keyword: drug development, drug mechanism,cancer, ClpP

Lee Graves
contact affiliation	Department of Pharmacology, The University of North Carolina at Chapel Hill
contact email	lmg@med.unc.edu
lab head
Laura Herring
contact affiliation	UNC-Chapel Hill
contact email	laura_herring@med.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038990
     1. Label: PRIDE project
     2. Name: Proteomics and phosphoproteomics analysis of SUM159 cells upon ClpP activation with ONC201 and TR57 compounds