Redox regulation of type-I inositol trisphosphate receptors in intact mammalian cells

The mechanism of cellular transformation by the human T-cell leukemia viruses (HTLVs) is thought to involve a novel retrovirus gene known as chi. The chi gene is essential for HTLV replication and acts by enhancing transcription from the viral long terminal repeat. By using the HTLV type I and II chi gene-coding regions inserted into a highly efficient expression vector, we directly compared the efficiencies of the two chi proteins to trans activate the HTLV type I and II long terminal repeats. We demonstrate that the two chi proteins have different patterns of trans activation. The patterns were highly reproducible in all mammalian cells tested. A different pattern of activation was observed in avian cells. These results suggest that the mechanism of trans activation involves specific cellular factors that are highly conserved throughout mammalian species but different in avian cells. Understanding the mechanism of trans activation by the chi gene product may provide insights into mechanisms of cellular transformation by HTLV.

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Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic Interplay Involving All Phases of the Viral Life Cycle

Current HIV Research ◽

10.2174/1570162x16666180817115830 ◽

2018 ◽

Vol 16 (3) ◽

pp. 184-207 ◽

Cited By ~ 9

Author(s):

Vanessa D`Urbano ◽

Elisa De Crignis ◽

Maria Carla Re

Keyword(s):

Mammalian Cells ◽

Viral Evolution ◽

Type I ◽

Restriction Factors ◽

Host Restriction ◽

Host Restriction Factors ◽

Immunodeficiency Virus ◽

Lentiviral Infection ◽

Specific Proteins ◽

Hiv 1

Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In the presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus. The identification and characterization of RFs have provided unique insights into the molecular biology of HIV-1, further revealing the complex host-pathogen interplay that characterizes the infection. The presence of RFs drove viral evolution, forcing the virus to develop specific proteins to counteract their activity. The knowledge of the mechanisms that prevent viral infection and their viral counterparts may offer new insights to improve current antiviral strategies. This review provides an overview of the RFs targeting HIV-1 replication and the mechanisms that regulate their expression as well as their impact on viral replication and the clinical course of the disease.

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Pretreatment with d-myo-Inositol Trisphosphate Reduces Infarct Size in Rabbit Hearts: Role of Inositol Trisphosphate Receptors and Gap Junctions in Triggering Protection

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.105.087742 ◽

2005 ◽

Vol 314 (3) ◽

pp. 1386-1392 ◽

Cited By ~ 18

Author(s):

Karin Przyklenk ◽

Michelle Maynard ◽

Chad E. Darling ◽

Peter Whittaker

Keyword(s):

Gap Junctions ◽

Infarct Size ◽

Inositol Trisphosphate ◽

Inositol Trisphosphate Receptors

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Reactive oxygen species oxidize STING and suppress interferon production

eLife ◽

10.7554/elife.57837 ◽

2020 ◽

Vol 9 ◽

Author(s):

Lili Tao ◽

Andrew Lemoff ◽

Guoxun Wang ◽

Christina Zarek ◽

Alexandria Lowe ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Reactive Oxygen ◽

Interferon Response ◽

Cellular Respiration ◽

Type I ◽

Oxygen Species ◽

Interferon Production ◽

Dna Sensing ◽

Cytoplasmic Dna

Reactive oxygen species (ROS) are by-products of cellular respiration that can promote oxidative stress and damage cellular proteins and lipids. One canonical role of ROS is to defend the cell against invading bacterial and viral pathogens. Curiously, some viruses, including herpesviruses, thrive despite the induction of ROS, suggesting that ROS are beneficial for the virus. However, the underlying mechanisms remain unclear. Here, we found that ROS impaired interferon response during murine herpesvirus infection and that the inhibition occurred downstream of cytoplasmic DNA sensing. We further demonstrated that ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine stimulator of interferon genes (STING), an ER-associated protein that mediates interferon response after cytoplasmic DNA sensing. This inhibited STING polymerization and activation of downstream signaling events. These data indicate that redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STING, controls interferon production. Together, our findings reveal that ROS orchestrates anti-viral immune responses, which can be exploited by viruses to evade cellular defenses.

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Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.741599 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuying Ma ◽

Xiaohui Wang ◽

Weisheng Luo ◽

Ji Xiao ◽

Xiaowei Song ◽

...

Keyword(s):

Dna Binding ◽

Mammalian Cells ◽

Rna Binding ◽

Binding Protein ◽

Structural Similarity ◽

Antiviral Response ◽

Binding Activity ◽

Type I Interferons ◽

Type I ◽

Innate Antiviral Response

cGAS, a DNA sensor in mammalian cells, catalyzes the generation of 2’-3’-cyclic AMP-GMP (cGAMP) once activated by the binding of free DNA. cGAMP can bind to STING, activating downstream TBK1-IRF-3 signaling to initiate the expression of type I interferons. Although cGAS has been considered a traditional DNA-binding protein, several lines of evidence suggest that cGAS is a potential RNA-binding protein (RBP), which is mainly supported by its interactions with RNAs, RBP partners, RNA/cGAS-phase-separations as well as its structural similarity with the dsRNA recognition receptor 2’-5’ oligoadenylate synthase. Moreover, two influential studies reported that the cGAS-like receptors (cGLRs) of fly Drosophila melanogaster sense RNA and control 3′-2′-cGAMP signaling. In this review, we summarize and discuss in depth recent studies that identified or implied cGAS as an RBP. We also comprehensively summarized current experimental methods and computational tools that can identify or predict RNAs that bind to cGAS. Based on these discussions, we appeal that the RNA-binding activity of cGAS cannot be ignored in the cGAS-mediated innate antiviral response. It will be important to identify RNAs that can bind and regulate the activity of cGAS in cells with or without virus infection. Our review provides novel insight into the regulation of cGAS by its RNA-binding activity and extends beyond its DNA-binding activity. Our review would be significant for understanding the precise modulation of cGAS activity, providing the foundation for the future development of drugs against cGAS-triggering autoimmune diseases such as Aicardi-Gourtières syndrome.

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Myosin 1E coordinates actin assembly and cargo trafficking during clathrin-mediated endocytosis

Molecular Biology of the Cell ◽

10.1091/mbc.e11-04-0383 ◽

2012 ◽

Vol 23 (15) ◽

pp. 2891-2904 ◽

Cited By ~ 57

Author(s):

Jackie Cheng ◽

Alexandre Grassart ◽

David G. Drubin

Keyword(s):

Mammalian Cells ◽

Actin Polymerization ◽

Type I ◽

Actin Assembly ◽

Significant Delay ◽

Src Homology 3 ◽

Integral Role ◽

Src Homology 3 Domain ◽

Src Homology ◽

Endocytic Vesicles

Myosin 1E (Myo1E) is recruited to sites of clathrin-mediated endocytosis coincident with a burst of actin assembly. The recruitment dynamics and lifetime of Myo1E are similar to those of tagged actin polymerization regulatory proteins. Like inhibition of actin assembly, depletion of Myo1E causes reduced transferrin endocytosis and a significant delay in transferrin trafficking to perinuclear compartments, demonstrating an integral role for Myo1E in these actin-mediated steps. Mistargeting of GFP-Myo1E or its src-homology 3 domain to mitochondria results in appearance of WIP, WIRE, N-WASP, and actin filaments at the mitochondria, providing evidence for Myo1E's role in actin assembly regulation. These results suggest for mammalian cells, similar to budding yeast, interdependence in the recruitment of type I myosins, WIP/WIRE, and N-WASP to endocytic sites for Arp2/3 complex activation to assemble F-actin as endocytic vesicles are being formed.

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