{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ILRUN (inflammation and lipid regulator with UBA‐like and NBR1‐like domains, formerly known as C6orf106) is a highly conserved protein that plays multifaceted roles in human physiology. At the molecular level, ILRUN is best characterized as a negative regulator of innate immunity. It inhibits the transcription of key antiviral and proinflammatory cytokines – including type‐I interferons (IFN‐α/β) and tumor necrosis factor α (TNFα) – by interacting with interferon regulatory factor 3 (IRF3) and impairing its recruitment to type‐I IFN promoter sequences, in addition to reducing the nuclear levels of important coactivators such as p300 and CBP. Both its UBA‐like and NBR1‐like domains are essential for this inhibitory function, with the crystal structure of the NBR1‐like domain providing further insight into its molecular architecture and potential mechanisms of action."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in modulating the antiviral inflammatory response, genetic studies have linked ILRUN to metabolic regulation. Variants in or near ILRUN (C6orf106) have been associated with alterations in body mass index (BMI) and longitudinal changes in lipid traits, suggesting that ILRUN may contribute to the regulation of lipid metabolism and obesity‐related phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, aberrant expression of ILRUN has been implicated in tumorigenesis. Elevated levels of ILRUN (C6orf106) have been observed in several cancers – including invasive breast cancer, non‐small cell lung cancer, and pancreatic cancer – where its overexpression is correlated with enhanced proliferation and invasion, as well as with markers of epithelial‐mesenchymal transition. These findings point to a potential oncogenic role for ILRUN in promoting tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, ILRUN functions as an important modulator balancing antiviral and inflammatory responses while also being linked to metabolic regulation and cancer progression. Additional studies into ILRUN’s biochemical interactions and regulatory networks will be critical for understanding its roles in health and disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Rebecca L Ambrose, Aaron M Brice, Alessandro T Caputo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular characterisation of ILRUN, a novel inhibitor of proinflammatory and antimicrobial cytokines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heliyon (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.heliyon.2020.e04115"}], "href": "https://doi.org/10.1016/j.heliyon.2020.e04115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32518853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32518853"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rebecca L Ambrose, Yu Chih Liu, Timothy E Adams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C6orf106 is a novel inhibitor of the interferon-regulatory factor 3-dependent innate antiviral response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA117.001491"}], "href": "https://doi.org/10.1074/jbc.RA117.001491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29802199"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29802199"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "S Ahmad, A Poveda, D Shungin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Obes (Lond) (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ijo.2016.72"}], "href": "https://doi.org/10.1038/ijo.2016.72"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27121252"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27121252"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Thomas J Baranski, Aldi T Kraja, Jill L Fink, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A high throughput, functional screen of human Body Mass Index GWAS loci using tissue-specific RNAi Drosophila melanogaster crosses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1007222"}], "href": "https://doi.org/10.1371/journal.pgen.1007222"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29608557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29608557"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shafqat Ahmad, Wei Zhao, Frida Renström, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-015-0259-x"}], "href": "https://doi.org/10.1186/s12881-015-0259-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26683835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26683835"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Guiyang Jiang, Xiupeng Zhang, Yong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel biomarker C6orf106 promotes the malignant progression of breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3500-5"}], "href": "https://doi.org/10.1007/s13277-015-3500-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25953261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25953261"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiupeng Zhang, Yuan Miao, Xinmiao Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C6orf106 enhances NSCLC cell invasion by upregulating vimentin, and downregulating E-cadherin and P120ctn."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-3274-9"}], "href": "https://doi.org/10.1007/s13277-015-3274-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25736925"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25736925"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Xin Li, Ming Dong, Jianping Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C6orf106 accelerates pancreatic cancer cell invasion and proliferation via activating ERK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-018-3455-0"}], "href": "https://doi.org/10.1007/s11010-018-3455-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30311108"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30311108"}]}]}]}