{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325129/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325129"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"A multi-subunit capture complex facilitates degradation of ER stalled MHC-I in pancreatic cancer","description":"Pancreatic ductal adenocarcinoma (PDAC) evades immune surveillance partly through autophagic capture and lysosomal degradation of major histocompatibility complex class I (MHC-I). However, the basis for this susceptibility remains unclear. Using synchronized ER exit assays, we show that PDAC cells retain MHC-I in the endoplasmic reticulum and inefficiently traffic it to the plasma membrane. An autophagic capture complex composed of the ER-phagy receptor TEX264 and the cargo receptor NBR1 mediates targeting of MHC-I for lysosomal degradation. Suppression of either receptor restores MHC-I levels and increases surface presentation. Binding of MHC-I to the capture complex is linked to antigen presentation efficiency as inhibition of antigen loading enhances MHC-I binding to the TEX264–NBR1 complex, whereas expression of high-affinity ER-targeted peptides reduces binding and promotes surface localization. A genome-wide CRISPRi screen identified the ER-resident E3 ligase NFXL1 as a mediator of MHC-I ubiquitylation and autophagic capture. Elevated NFXL1 correlates with reduced MHC-I expression and poor patient prognosis, highlighting a targetable pathway regulating PDAC immunogenicity.","dates":{"publication":"2026/07/22"},"accession":"GSE325129","cross_references":{"GSM":["GSM9596511","GSM9596510"],"GPL":["20301"],"GSE":["325129"],"taxon":["Homo sapiens"],"PMID":["[42214332]"]}}