PXD060575

PXD060575 is an original dataset announced via ProteomeXchange.

Title	ERAP1 activity modulates the immunopeptidome but also affects the proteome, metabolism and stress responses in cancer cells
Description	Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) metabolizes peptides inside the ER and shapes the peptide repertoire available for binding to Major Histocompatibility Complex Class I molecules (MHC-I). Moreover, it may have additional effects on cellular homeostasis, which have not been explored. To address these questions, we used both genetic silencing of ERAP1 expression as well as treatment with 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 with both methods of functional ERAP1 disruption, which were distinct for each method. Both methods of inhibition led to an enhancement, albeit slight, in tumor cell killing by stimulated human PBMCs and in significant proteomic alterations in 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 sensitivity to 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 9.6% of differentially presented peptides belonged to proteins with altered expression and only 4.0% of proteins with altered expression were represented in the immunopeptidome shifts. Taken together, our findings suggest that modulation of ERAP1 activity can generate unique immunopeptidomes, mainly due to altered peptide processing in the ER, but also induce changes in the cellular proteome and metabolic state which may have further effects on tumor cells.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-26_03:24:00.060.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	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-07 01:49:54	ID requested
⏵ 1	2025-05-26 03:24:00	announced

10.1016/J.MCPRO.2025.100964;

submitter keyword: cancer, proteomics,ERAP1, THP1 cells

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

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PRIDE project URI

• PRIDE
  1. PXD060575
     1. Label: PRIDE project
     2. Name: ERAP1 activity modulates the immunopeptidome but also affects the proteome, metabolism and stress responses in cancer cells