PXD048728-2

PXD048728 is an original dataset announced via ProteomeXchange.

Title	Tapasin assembly surveillance by the RNF185/MBRL ubiquitin ligase complex regulates MHC-I antigen presentation
Description	Immune surveillance by cytotoxic T cells eliminates tumor cells and cells infected by intracellular pathogens. This process relies on the presentation of antigenic peptides on Major Histocompatibility Complex class I (MHC-I) at the cell surface. The loading of these peptides onto MHC-I depends on the peptide loading complex (PLC) at the endoplasmic reticulum (ER). Here, we uncovered that MHC-I antigen presentation is regulated by ER-associated degradation (ERAD), a protein quality control process essential to clear misfolded and unassembled proteins. An unbiased proteomics screen identified the PLC component Tapasin, essential for peptide loading onto MHC-I, as a substrate of the RNF185/Membralin ERAD complex. Loss of RNF185/MBRL resulted in elevated Tapasin steady state levels and increased MHC-I at the surface of professional antigen presenting cells. We further show that RNF185/MBRL ERAD complex recognizes unassembled Tapasin and limits its incorporation into PLC. These findings establish a novel mechanism controlling antigen presentation and suggest RNF185/Membralin as potential therapeutic targets to modulate immune surveillance.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:58:52.006.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pedro Carvalho
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-20 03:49:36	ID requested
1	2024-09-17 09:29:49	announced
⏵ 2	2024-10-22 06:58:52	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: RNF185 MBRL Tapasin

Pedro Carvalho
contact affiliation	Sir William Dunn School of Pathology, University of Oxford, UK
contact email	pedro.carvalho@path.ox.ac.uk
lab head
Pedro Carvalho
contact affiliation	University of Oxford
contact email	pedro.carvalho@path.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048728
     1. Label: PRIDE project
     2. Name: Tapasin assembly surveillance by the RNF185/MBRL ubiquitin ligase complex regulates MHC-I antigen presentation