PXD025501
PXD025501 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Systematic evaluation and modulation of HLA class I downregulation in Merkel cell carcinoma |
Description | Lee 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. |
HostingRepository | MassIVE |
AnnounceDate | 2022-06-29 |
AnnouncementXML | Submission_2022-06-29_07:41:59.535.xml |
DigitalObjectIdentifier | |
ReviewLevel | Non peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Karl Clauser |
SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
ModificationList | unknown modification; unknown modification; unknown modification; unknown modification; unknown modification |
Instrument | Orbitrap Fusion Lumos; Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2021-04-20 20:15:03 | ID requested | |
⏵ 1 | 2022-06-29 07:41:59 | announced |
Publication List
no publication |
Keyword List
submitter keyword: TMT, Merkel cell carcinoma, immunopeptidomics |
Contact List
Steven A. Carr | |
---|---|
contact affiliation | Broad Institute of MIT and Harvard |
contact email | scarr@broadinstitute.org |
lab head | |
Karl Clauser | |
contact affiliation | Broad Institute of MIT and Harvard |
contact email | clauser@broadinstitute.org |
dataset submitter |
Full Dataset Link List
MassIVE dataset URI |
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://massive.ucsd.edu/MSV000087251/ |