PXD054494

PXD054494 is an original dataset announced via ProteomeXchange.

Title	ERAP1 as a regulator of the immunopeptidome, proteome and cellular homeostasis of cancer cells. Immunopeptdome_PartII
Description	Endoplasmic reticulum aminopeptidase 1 (ERAP1) metabolizes peptides inside the ER and shapes the peptide repertoire available for binding to Major Histocompatibility Class I molecules (MHC-I). Moreover, it may have additional effects on cellular homeostasis, which have not been explored. To address these questions, we utilized genetic silencing of ERAP1 expression as well as a selective allosteric ERAP1 inhibitor to probe changes in the immunopeptidome and proteome of the A375 melanoma cancer cell line. We observed significant immunopeptidome shifts upon both methods of ERAP1 functional disruption, which were distinct for each method. Both methods of inhibition led to mild enhancement of cancer cell killing by stimulated human PBMCs from a healthy donor. ERAP1 functional disruption also resulted in significant proteomic alterations that focused on pathways related to metabolism and cellular stress. Similar proteomic changes were also observed in the leukemia cell line THP-1. Biochemical analyses suggested that ERAP1 inhibition affected ER stress, reactive oxygen species production and mitochondrial metabolism. Although the proteomics shifts were significant, their potential in shaping immunopeptidome shifts was limited since only 15.8% of differentially presented peptides belonged to proteins with altered expression and 4.8% of proteins with altered expression were represented in the immunopeptidome shifts. Taken together, our findings suggest that inhibition of ERAP1 can generate unique immunopeptidomes, primarily due to altered peptide processing in the ER, but also induce compensatory changes in the cellular proteome and metabolic state which may have additional effects on cancer cells.
HostingRepository	PRIDE
AnnounceDate	2025-05-23
AnnouncementXML	Submission_2025-05-23_06:43:03.946.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Samiotaki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-01 05:15:22	ID requested
⏵ 1	2025-05-23 06:43:04	announced

10.1016/J.MCPRO.2025.100964;

submitter keyword: Cancer,ERAP1, antigen presentation, Proteomics, MHC-I, Immunopeptidomics, antigen trimming

Efstratios Stratikos
contact affiliation	Department of Chemistry, National and Kapodistrian University of Athens, 15784 Zografou, Greece
contact email	estratikos@chem.uoa.gr
lab head
Martina Samiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD054494

PRIDE project URI

• PRIDE
  1. PXD054494
     1. Label: PRIDE project
     2. Name: ERAP1 as a regulator of the immunopeptidome, proteome and cellular homeostasis of cancer cells. Immunopeptdome_PartII