Small-molecule modulators of INAVA cytosolic condensate and cell-cell junction assemblies.

ABSTRACT: Epithelial cells lining mucosal surfaces distinctively express the inflammatory bowel disease risk gene INAVA. We previously found that INAVA has dual and competing functions: one at lateral membranes where it affects mucosal barrier function and the other in the cytosol where INAVA enhances IL-1β signal transduction and protein ubiquitination and forms puncta. We now find that IL-1β-induced INAVA puncta are biomolecular condensates that rapidly assemble and physiologically resolve. The condensates contain ubiquitin and the E3 ligase βTrCP2, and their formation correlates with amplified ubiquitination, suggesting function in regulation of cellular proteostasis. Accordingly, a small-molecule screen identified ROS inducers, proteasome inhibitors, and inhibitors of the protein folding chapero

SUBMITTER: Chang D 

PROVIDER: S-EPMC8276315 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature