PXD070359

PXD070359 is an original dataset announced via ProteomeXchange.

Title	CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans - human CMTM6 interactome
Description	The transmembrane protein CMTM6 promotes plasma membrane expression of immune checkpoint PD-L1, an important suppressor of anti-tumor immunity. Targeting of CMTM6 was proposed as a strategy to decrease surface PD-L1 and trigger cytotoxicity against tumors. In accord, ablation of CMTM6 in mouse cancer models was shown to efficiently suppress tumor growth in a manner partially independent of PD-L1, which suggested that CMTM6 might regulate other proteins involved in anti-tumor immunity. Using mass spectrometry, we discovered that mouse CMTM6 strongly associates with the cell death receptor FAS and negatively regulates its expression in mice. Deletion of CMTM6 promotes FAS membrane localization and renders murine cells sensitive to FAS ligand-induced cytotoxicity. However, the interaction between CMTM6 and FAS is lost in human cells due to the difference in three amino acids at the boundary of the FAS extracellular and transmembrane domains. Altogether, our data urge caution when transferring promising data regarding the targeting of CMTM6 from mouse cancer models to potential human therapies. This dataset contains the MS analysis of proteins associated with human CMTM6. Human CMTM6 or control EGFP were fused to the SF-tag, stably expressed in mouse ST2 cells, and isolated via tandem affinity purification.
HostingRepository	PRIDE
AnnounceDate	2026-03-16
AnnouncementXML	Submission_2026-03-16_03:48:34.943.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Draber
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-05 08:00:43	ID requested
⏵ 1	2026-03-16 03:48:36	announced

Semberova T, Pribikova M, Cimermanova V, Trivic T, Haderbache R, Paprckova D, Christen L, Kissiova H, Stepanek O, Draber P, CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans. EMBO Rep, 27(5):1301-1324(2026) [pubmed]

10.1038/s44319-026-00694-8;

submitter keyword: CD58,CMTM6

Peter Draber
contact affiliation	Department of Immunobiology, University of Lausanne, Epalinges, Switzerland
contact email	peter.draber@unil.ch
lab head
Peter Draber
contact affiliation	BIOCEV, First Faculty of Medicine, Charles University
contact email	peter.draber@lf1.cuni.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070359
     1. Label: PRIDE project
     2. Name: CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans - human CMTM6 interactome