Open AccessJournal Article
DDX41 recognizes bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune response (P1375)
Kislay Parvatiyar,Zhiqiang Zhang,Rosane M. B. Teles,Songying Ouyang,Yan Jiang,Zhi-Jie Liu,Shankar S. Iyer,Shivam A. Zaver,Mirjam Schenk,Shang Zeng,Wenwan Zhong,Robert L. Modlin,Yongjun Liu,Genhong Cheng +13 more
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In this article, the authors identify the helicase, DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41) as the pattern recognition receptor (PRR) that senses both cyclic-di-GMP and cyclic -di-AMP.Abstract:
Cytosolic detection of bacterially derived secondary messengers cyclic-di-GMP (c-di-GMP) or cyclic -di-AMP (c-di-AMP) by the host immune system activates an innate immune response characterized by the induction of type I interferons (IFNs) Induction of IFN by c-di-GMP or c-di-AMP has been shown to be dependent on a stimulator of IFN genes-TANK binding kinase 1-IFN regulatory factor 3 (STING-TBK1-IRF3) signaling axis Although STING has been shown to interact with c-di-GMP, an upstream sensor of these cyclic dinucleotides is unknown Here we identify the helicase, DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41) as the pattern recognition receptor (PRR) that senses both c-di-GMP and c-di-AMP DDX41 specifically and directly interacts with c-di-GMP Knockdown of DDX41 via shRNA in murine or human immune cells inhibits the induction of innate immune genes and results in defective STING, TBK1 and IRF3 activation in response to c-di-GMP or c-di-AMP Our findings suggest a mechanism whereby c-di-GMP and c-di-AMP molecules are detected by the DDX41 PRR, which complexes with the STING adaptor to signal to TBK1-IRF3 and activate the IFN responseread more
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Biological implications of somatic DDX41 p.R525H mutation in acute myeloid leukemia
Moe Kadono,Akinori Kanai,Akiko Nagamachi,Satoru Shinriki,Jin Kawata,Koji Iwato,Taiichi Kyo,Kumi Oshima,Akihiko Yokoyama,Takeshi Kawamura,Reina Nagase,Daichi Inoue,Toshio Kitamura,Toshiya Inaba,Tatsuo Ichinohe,Hirotaka Matsui,Hirotaka Matsui +16 more
TL;DR: A pathogenic role of p.R525H DDX41 in the slow growth rate of tumor cells is uncovered, which causes a certain ribosomopathy phenotype in hematopoietic cells by suppressing MDM2-mediated RB degradation, thus triggering the inhibition of E2F activity.
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Functional analysis of the sporulation-specific diadenylate cyclase CdaS in Bacillus thuringiensis.
TL;DR: This study demonstrated that CdaS protein from B. thuringiensis is a hexameric DAC protein that can convert ATP or ADP to c-di-AMP in vitro and the N-terminal YojJ domain is essential for the DAC activity.
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Human DExD/H RNA helicases: Emerging roles in stress survival regulation
Jing Wen Shih,Yan-Hwa Wu Lee +1 more
TL;DR: Current knowledge on major mechanistic themes of human DExD/H RNA helicases in response to stressful stimuli is outlined, especially on emerging molecular models for the functional roles of these enzymes in the stress survival regulation.
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Detection of cyclic di-AMP using a competitive ELISA with a unique pneumococcal cyclic di-AMP binding protein
TL;DR: A competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of c-di-AMP was developed using a novel pneumococcal c- Di-AMP binding protein (CabP) to ensure that c-Di-AMP concentrations in biological samples can be quickly and accurately quantified.
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Unabated Adenovirus Replication following Activation of the cGAS/STING-Dependent Antiviral Response in Human Cells
Eric Lam,Erik Falck-Pedersen +1 more
TL;DR: This study shows for the first time that the cGAS DNA sensor directs a dominant IRF3/IFN/ISG antiviral response to adenovirus in human cell lines.
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