蛋白质稳态
生物
胞浆
细胞生物学
泛素连接酶
泛素
信号转导
生物物理学
细胞
细胞内
小分子
细胞膜
生物化学
基因
酶
作者
Denis Chang,Phi Luong,Qian Li,Jamie LeBarron,Michael D. Anderson,Lee Barrett,Wayne I. Lencer
标识
DOI:10.1083/jcb.202007177
摘要
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 chaperone HSP90 as potent agonists for INAVA condensate formation. Notably, inhibitors of the p38α and mTOR pathways enhanced resolution of the condensates, and inhibitors of the Rho-ROCK pathway induced INAVA's competing function by recruiting INAVA to newly assembled intercellular junctions in cells where none existed before.
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