生物
STAT1
车站2
磷脂酰肌醇
STAT蛋白
激酶
先天免疫系统
效应器
信号转导
干扰素
抄写(语言学)
细胞生物学
转录因子
免疫系统
车站3
基因
遗传学
语言学
哲学
作者
Chinmoy Ghosh,Ruchi Kakar,Rosalie G. Hoyle,Zheng Liu,Chunqing Guo,Jiong Li,Xiang‐Yang Wang,Yue Sun
标识
DOI:10.1016/j.devcel.2024.02.005
摘要
The interferon signaling pathway is critical for host defense by serving diverse functions in both innate and adaptive immune responses. Here, we show that type I gamma phosphatidylinositol phosphate 5-kinase i5 (PIPKIγi5), an enzyme that synthesizes phosphatidylinositol-4,5-bisphosphate (PI4,5P2), controls the sensitivity to interferon in both human and mouse cells. PIPKIγi5 directly binds to the interferon-gamma (IFN-γ) downstream effector signal transducer and activator of transcription 1 (STAT1), which suppresses the STAT1 dimerization, IFN-γ-induced STAT1 nuclear translocation, and transcription of IFN-γ-responsive genes. Depletion of PIPKIγi5 significantly enhances IFN-γ signaling and strengthens an antiviral response. In addition, PIPKIγi5-synthesized PI4,5P2 can bind to STAT1 and promote the PIPKIγi5-STAT1 interaction. Similar to its interaction with STAT1, PIPKIγi5 is capable of interacting with other members of the STAT family, including STAT2 and STAT3, thereby suppressing the expression of genes mediated by these transcription factors. These findings identify the function of PIPKIγi5 in immune regulation.
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