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PXD029489 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRNF31 inhibition sensitizes tumors to bystander killing by innate and adaptive immune cells
DescriptionTumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8+ T cell antitumor activity. Although innate NK cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel genome-wide CRISPR-Cas9 screens. This identified all components, RNF31, RBCK1, and SHARPIN, of the linear ubiquitination chain assembly complex (LUBAC). Genetic and pharmacologic ablation of RNF31, an E3 ubiquitin ligase, strongly sensitized melanoma, breast and colorectal cancer cells to both NK and CD8+ T cell killing. This occurred in a TNF-dependent manner, causing loss of A20 and non-canonical IKK complexes from TNF Receptor Complex I. Corroborating this preclinically, a small molecule RNF31 inhibitor sensitized human colon carcinoma organoids to TNF and greatly enhanced immune bystander killing of antigen-loss and antigen presentation machinery-deficient tumor cells. These results merit exploration of RNF31 inhibition as a clinical pharmacological opportunity for immunotherapy-refractory cancers.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKelly Stecker
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-02 03:53:58ID requested
12022-05-30 00:36:23announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: TNF, RNF31, AP
Contact List
Maarten Altelaar
contact affiliationUtrecht University
contact emailm.altelaar@uu.nl
lab head
Kelly Stecker
contact affiliationUtrecht University
contact emailk.e.stecker@uu.nl
dataset submitter
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