2026-10-10T06:28:14Z https://api.figshare.com/v2/oai

oai:figshare.com:article/28646573 2026-09-14T08:09:24Z category_24778 item_type_3 month_year_09_2026

_{Datasets for the eLife manuscript"}_{ORMDL3 restrains type I interferon signaling and anti-tumor immunity by promoting RIG-I degradation"} Qi Zeng (20922783) Chen Yao (137375) Shimeng Zhang (20922826) Yizhi Mao (20922829) Jing Wang (20922832) Ziyang Wang (17796838) Chunjie Sheng (20922834) Shuai Chen (20922839) Cancer cell biology ORMDL3 RIG-I-like receptors signaling <p dir="ltr">Mounting evidence has demonstrated the genetic association of ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) gene polymorphisms with bronchial asthma and a diverse set of inflammatory disorders. However, its role in type I interferon (type I IFN) signaling remains poorly defined. Herein, we report that ORMDL3 is a negative modulator of the type I IFN signaling by interacting with mitochondrial antiviral signaling protein (MAVS) and subsequently promoting the proteasome-mediated degradation of retinoic acid-inducible gene I (RIG-I). Immunoprecipitation coupled with mass spectrometry (IP-MS) assays uncovered that ORMDL3 binds to ubiquitin-specific protease 10 (USP10), which forms a complex with and stabilizes RIG-I through decreasing its K48- linked ubiquitination. ORMDL3 thus disrupts the interaction between USP10 and RIG-I, thereby promoting RIG-I degradation. Additionally, subcutaneous syngeneic tumor models in C57BL/6 mice revealed that inhibition of ORMDL3 enhances anti-tumor efficacy by augmenting the proportion of cytotoxic CD8 positive T cells and IFN production in the tumor microenvironment (TME). Collectively, our findings reveal the pivotal roles of ORMDL3 in maintaining antiviral innate immune responses and anti-tumor immunity.</p> 2025-03-24T02:39:13Z Dataset Dataset 10.6084/m9.figshare.28646573.v3 https://figshare.com/articles/dataset/_sub_Datasets_for_the_eLife_manuscript_sub_sub_ORMDL3_restrains_type_I_interferon_signaling_and_anti-tumor_immunity_by_promoting_RIG-I_degradation_sub_/28646573 CC BY 4.0