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PXD025501

PXD025501 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSystematic evaluation and modulation of HLA class I downregulation in Merkel cell carcinoma
DescriptionLee PC, Klaeger S, Le PM, Korthauer K, Cheng J, Wong A, Tarren A, Lemvigh C, Sarkizova S, Li L, Frost TC, Nomburg J, Liu X, Pomerance L, Doherty L, Witten E, Zhang W, Apffel A, Wallace L, Neuberg D, Olsen L, Thakuria M, Clauser K, Starrett G, Doench J, Buhrlage SJ, Carr SA, DeCaprio JA, Wu CJ, Keskin DB. 2021 Viruses avoid immune surveillance through an array of mechanisms, including perturbation of HLA class I (HLA I) antigen presentation. Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer often caused by the Merkel cell polyomavirus (MCPyV) that exhibits low HLA class I surface expression. Through the characterization of 11 newly generated MCC cell lines, we identified multiple class I defects including transcriptional suppression of HLA I genes and NLRC5 alterations. To systematically identify regulators of HLA I loss in MCC, we performed parallel genome-scale gain- and loss-of-function screens in an MCPyV-positive line and identified the noncanonical Polycomb repressive complex PRC1.1 and MYCL as HLA I suppressors. Both hits interact with MCPyV viral antigens, and pharmacologic inhibition of PRC1.1 component USP7 resulted in HLA I upregulation. These findings establish a mechanism for MCPyV-mediated HLA class I suppression and identify therapeutic targets for HLA restoration in MCC.
HostingRepositoryMassIVE
AnnounceDate2022-06-29
AnnouncementXMLSubmission_2022-06-29_07:41:59.535.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKarl Clauser
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListunknown modification; unknown modification; unknown modification; unknown modification; unknown modification
InstrumentOrbitrap Fusion Lumos; Q Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-20 20:15:03ID requested
12022-06-29 07:41:59announced
Publication List
no publication
Keyword List
submitter keyword: TMT, Merkel cell carcinoma, immunopeptidomics
Contact List
Steven A. Carr
contact affiliationBroad Institute of MIT and Harvard
contact emailscarr@broadinstitute.org
lab head
Karl Clauser
contact affiliationBroad Institute of MIT and Harvard
contact emailclauser@broadinstitute.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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