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Paper Reading 01 KAT8 selectively inhibits antiviral immunity by acetylating IRF3 Wanwan Huai, Xingguang Liu, Chunmei Wang, et al.. J.Exp. Med. 2019 Optimal activation of innate immune response is crucial for maintaining immune homeostasis and the elimination of invading pathogens, which involves diverse signaling pathway regulation and post translational modifications (PTMs). In this paper the author reveals a critical role for KAT8 and IRF3 lysine acetylationin the suppression of antiviral innate immunity. At first, Using siRNA targeting 5 MYST members for functional screening, the authors found that deficiency in KAT8 selectively promotes the production of IFN-I. The data showed that KAT8 selectively inhibited IFN-1 production in macrophages and DCS induced by RNA and DNA virus infection. Then, the researchers found that KAT8-deficient micehad a significantly higher survival rate than their KAT8-deficientmice. KAT8-deficient mice also produced more IFN-α and IFN-β in response to VSV infection. Therefore, KAT8 lacks the ability to protect mice from virus attack by selectively promoting IFN-1 production. In order to further explore the mechanism of KAT8 in antiviral immunity, the author found that KAT8 could bind to IRF3 through the experimental method of immuno precipitation combined with mass spectrometry, and confirmed the interaction between the two in vivo and in vitro binding experiments. Through subsequent overexpression, knocking down KAT8 and combined with acetylated antibody test, the authors found that KAT8 could indeed promote the acetylated regulation of IRF3 in the process of virus infection through its acetyl transferase activity. Inconclusion, this study provides a novel PTM layer of IRF3 that can attenuate antiviral innate immunity. Inhibition of KAT8 expression may be a promising intervention for treating viral diseases. 10.1084/jem.20181773 02 Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy Penghua Yang ,Cheng Xu1, E. Albert Reece , et al.. Nature Communication 2019 Myristoylated Alanine-Rich C Kinase Substrate(MARCKS) is required for neural tube closure, however, the regulation and of its biological activity and function have remained elusive. The author found that high maternal glucose induced MARCKS acetylation at lysine 165 by the acetyl transferase Tip60, which is a prerequisite for its phosphorylation, whereas Sirtuin 2 (SIRT2) deacetylated MARCKS. Phosphorylated MARCKS dissociates from organelles, leading to mitochondrial abnormalities and endoplasmic reticulum stress. Phosphorylation dead MARCKS ( PD-MARCKS) reversed maternal diabetes-induced cellular organelle stress, apoptosis and delayed neurogenesis in the neuroepithelium and ameliorated neural tube defects. Restoring SIRT2 expression in the developing neuroepithelium exerted identical effects as those of PD-MARCKS. In conclusion, this study reveal a new regulatory mechanism for MARCKS acetylation and phosphorylation that disrupts neurulation under diabetic conditions by diminishing the cellular organelle protective effect of MARCKS. https:///10.1038/s41467-018-08268-6 END |
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