E3 ligase c-Cbl regulates intestinal inflammation through suppressing fungi-induced noncanonical NF-κB activation
Jielin Duan, Hui-Qian He, Yao Yu, Tao Liu, Shu-Jun Ma, Dedong Li, Yan-Shan Jiang, Xin Lin, Dedong Li, Quanzhen Lv, Huihui Ma, Xin‐Ming Jia
Abstract
, thereby aggravating DSS-induced colitis. Moreover, suppressing fungal growth with fluconazole or inhibition of RelB activation in vivo attenuates colitis in mice with DC-specific deletion of c-Cbl. We also demonstrate an interaction between c-Cbl and c-Abl tyrosine kinase and find that treatment with DPH, a c-Abl agonist, synergistically increases fungi-induced c-Cbl activation to restrict colitis. Together, these findings unravel a previously unidentified fungi-induced c-Cbl/RelB axis that sustains intestinal homeostasis and protects against intestinal inflammation.
Topics & Concepts
RELBUbiquitin ligaseCell biologyInflammationHomeostasisNF-κBChemistryDNA ligaseUbiquitinNFKB1MicrobiologyBiologyBiochemistrySignal transductionImmunologyEnzymeTranscription factorGeneNF-κB Signaling PathwaysPeptidase Inhibition and AnalysisCancer Research and Treatments