The cytoplasmic domain of the pseudoprotease iRhom2 mediates distinct signaling mechanisms to control activation of the cell surface protease ADAM17.

ABSTRACT: ADAM17 is a cell surface protease that controls the release of the ectodomains of signaling proteins, including epidermal growth factor receptor ligands and the primary inflammatory cytokine tumor necrosis factor. Reflecting this important role in signaling, dysregulated ADAM17 activity is linked to many human diseases, including immunodeficiency, inflammatory bowel disease, rheumatic arthritis, cancer, and Alzheimer's disease. iRhom2, a pseudoprotease of the rhomboid-like superfamily, has evolved to be a multifunctional regulatory cofactor of ADAM17. Recent structural and functional work has begun to reveal how the iRhom2 transmembrane and extracellular domains act to control ADAM17 activity. The cytoplasmic domain, however, remains less explored. Here, using a combination of proteomic, g

SUBMITTER: Lu F 

PROVIDER: S-EPMC12516561 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature