Ubiquitin ligase STUB1 destabilizes IFNγ-receptor complex to suppress tumor IFNγ signaling

• DOI: 10.1038/s41467-022-29442-x
• Publication Date: 2022-04-08T10:07:06Z
• Authors: Georgi Apriamashvili; David W. Vredevoogd; Oscar Krijgsman; Onno B. Bleijerveld; Maarten A. Ligten...; Beaunelle de Bruijn; Julia Boshuizen; Joleen J. H. Traets; Daniela D’Empaire...; Alex van Vliet; Chun-Pu Lin; Nils L. Visser; James D. Londino; Rebekah Sanchez-H...; Leah E. Oswalt; Selin Altinok; Jonathan C. Schisler; Maarten Altelaar; Daniel S. Peeper
• Keywords: Checkpoint Kinase 2

The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators IFNγ-R1 cell surface abundance, we identify STUB1 as E3 ubiquitin ligase in complex with signal-relaying kinase JAK1. mediates ubiquitination-dependent proteasomal degradation IFNγ-R1/JAK1 through