E3 ubiquitin-protein ligase RNF186

Definition:

E3 ubiquitin protein ligase that is part of an apoptotic signaling pathway activated by endoplasmic reticulum stress. Stimulates the expression of proteins specific of the unfolded protein response (UPR), ubiquitinates BNIP1 and regulates its localization to the mitochondrion and induces calcium release from the endoplasmic reticulum that ultimately leads to cell apoptosis. Plays a role in the maintenance of intestinal homeostasis and clearance of enteric pathogens. Upon NOD2 stimulation, ubiquitinates the ER stress sensor activating transcription factor 6/ATF6 and promotes the unfolded protein response UPR. Participates in basal level of autophagy maintenance by regulating the ubiquitination of EPHB2 and EPHB3. Upon stimulation by ligand EFNB1, ubiquitinates EPHB2 and further recruits MAP1LC3B for autophagy induction. Controls nutrient sensing by ubiquitinating Sestrin-2/SESN2, which is an intracellular sensor of cytosolic leucine and inhibitor of mTORC1 activity.

References:

[1]. Travis B Lear, et al. The RING-type E3 ligase RNF186 ubiquitinates Sestrin-2 and thereby controls nutrient sensing. J Biol Chem. 2019 Nov 8;294(45):16527-16534. [Content Brief]

[2]. Peng Wang, et al. A novel RING finger E3 ligase RNF186 regulate ER stress-mediated apoptosis through interaction with BNip1. Cell Signal. 2013 Nov;25(11):2320-33. [Content Brief]

[3]. Kishu Ranjan, et al. Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response. J Clin Invest. 2021 Sep 1;131(17):e145472. [Content Brief]

[4]. Huazhi Zhang, et al. RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis. Autophagy. 2021 Oct;17(10):3030-3047. [Content Brief]

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