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Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response

J Clin Invest. 2021-09; 
Kishu Ranjan, Matija Hedl, Saloni Sinha, Xuchen Zhang, Clara Abraham
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Mutagenesis Services p3xFLAG-hATF6 lysine mutants (K149A, K152A, K350A, and K356A) were generated through site-directed mutagenesis (GenScript) of the ATF6 parent vector and confirmed by sequencing Get A Quote

摘要

Properly balancing microbial responses by the innate immune system through pattern recognition receptors (PRRs) is critical for intestinal immune homeostasis. Ring finger protein 186 (RNF186) genetic variants are associated with inflammatory bowel disease (IBD). However, functions for the E3 ubiquitin ligase RNF186 are incompletely defined. We found that upon stimulation of the PRR nucleotide-binding oligomerization domain containing 2 (NOD2) in human macrophages, RNF186 localized to the ER, formed a complex with ER stress sensors, ubiquitinated the ER stress sensor activating transcription factor 6 (ATF6), and promoted the unfolded protein response (UPR). These events, in turn, led to downstream signaling, cyt... More

关键词

Immunology, Innate immunity, Macrophages