Palmitoylation of NOD1 and NOD2 is required for bacterial sensingThe nucleotide oligomerization domain (NOD)-like receptors 1 and 2 (NOD1/2) are intracellular pattern-recognition proteins that activate immune signaling pathways in response to peptidoglycans associated with microorganisms. Recruitment to bacteria-containing endosomes and other intracellular membranes is required for NOD1/2 signaling, and NOD1/2 mutations that disrupt membrane localization are associated with inflammatory bowel disease and other inflammatory conditions. However, little is known about this recruitment process. We found that NOD1/2 S-palmitoylation is required for membrane recruitment and immune signaling. ZDHHC5 was identified as the palmitoyltransferase responsible for this critical posttranslational modification, and several disease-associated mutations in NOD2 were found to be associated with defective S-palmitoylation. Thus, ZDHHC5-mediated S-palmitoylation of NOD1/2 is critical for their ability to respond to peptidoglycans and to mount an effective immune response.
CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunityPHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locusLi Chen, Qiaoqiao Tong, Xiaowen Chen et al.|Nature Communications|2021 Polycomb group (PcG) proteins maintain cell identity by repressing gene expression during development. Surprisingly, emerging studies have recently reported that a number of PcG proteins directly activate gene expression during cell fate determination process. However, the mechanisms by which they direct gene activation in pluripotency remain poorly understood. Here, we show that Phc1, a subunit of canonical polycomb repressive complex 1 (cPRC1), can exert its function in pluripotency maintenance via a PRC1-independent activation of Nanog. Ablation of Phc1 reduces the expression of Nanog and overexpression of Nanog partially rescues impaired pluripotency caused by Phc1 depletion. We find that Phc1 interacts with Nanog and activates Nanog transcription by stabilizing the genome-wide chromatin interactions of the Nanog locus. This adds to the already known canonical function of PRC1 in pluripotency maintenance via a PRC1-dependent repression of differentiation genes. Overall, our study reveals a function of Phc1 to activate Nanog transcription through regulating chromatin architecture and proposes a paradigm for PcG proteins to maintain pluripotency.
S-acylation of ATGL is required for lipid droplet homoeostasis in hepatocytes<i>S-</i> acylation of PNPLA2/ATGL: a necessity for triacylglycerol lipolysis and lipophagy in hepatocytesacyltransferase or expression of S-acylation deficient PNPLA2 mutants impairs not only lipolysis but also lipophagy. This finding suggests that the mere presence of PNPLA2 with its LC3-interacting region (LIR) motifs is insufficient to drive lipophagy without triacylglycerol breakdown. Our study provides insights into yet another mode of regulation of PNPLA2 activity with implications for understanding lipid droplet catabolism, lipophagy, and cellular energy homeostasis.