Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

Gui, Xiang; Yang, Hui; Li, Tuo; Tan, Xiaojun; Shi, Pilong; Li, Minghao; Du, Fenghe; Chen, Zhijian J.

doi:10.1038/s41586-019-1006-9

Cited by 872 publications

(1,061 citation statements)

References 28 publications

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“…Defective or absence of autophagy resulted in increased infection in the fly brain and death [96]. STING-dependent induction of protective autophagy was independently reported for DNA viruses and sea anemone, supporting an evolutionarily conserved role for STING in microbial autophagy [5].…”

Section: Autophagy-mediated Restriction Of +Rna Virus Infectionsmentioning

confidence: 71%

“…Besides, it is equipped to clear invasive pathogens through induction of CD8 + T-cell responses, and also initiates a primordial innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. This was recently described in the context of DNA virus infections, where cyclic GMP-AMP (cGAMP) and STING-dependent activation of autophagy was necessary to remove viral DNA from the cytosol [5]. However, in an ongoing evolutionary arms race, most pathogens have acquired the ability to hijack and subvert autophagy to evade degradation through this pathway.…”

Section: Introductionmentioning

confidence: 99%

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Manipulation of autophagy by (+) RNA viruses

Wong

Sanyal

2020

Seminars in Cell & Developmental Biology

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A B S T R A C TAutophagy is an evolutionarily conserved process central to host metabolism. Among its major functions are conservation of energy during starvation, recycling organelles, and turnover of long-lived proteins. Besides, autophagy plays a critical role in removing intracellular pathogens and very likely represents a primordial intrinsic cellular defence mechanism. More recent findings indicate that it has not only retained its ability to degrade intracellular pathogens, but also functions to augment and fine tune antiviral immune responses. Interestingly, viruses have also co-evolved strategies to manipulate this pathway and use it to their advantage. Particularly intriguing is infection-dependent activation of autophagy with positive stranded (+)RNA virus infections, which benefit from the pathway without succumbing to lysosomal degradation. In this review we summarise recent data on viral manipulation of autophagy, with a particular emphasis on +RNA viruses and highlight key unanswered questions in the field that we believe merit further attention. (S. Sanyal).Seminars in Cell and Developmental Biology xxx (xxxx) xxx-xxx 1084-9521/

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Section: Autophagy-mediated Restriction Of +Rna Virus Infectionsmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Manipulation of autophagy by (+) RNA viruses

Wong

Sanyal

2020

Seminars in Cell & Developmental Biology

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“…Recently, mounting evidence reveals that cGASeSTING pathway can activate autophagy robustly which is an ancient and highly conserved function predating the evolution of type I IFNs ( Fig. 1) [8,10,30]. Of note, cGAMP-induced autophagy can clear the cytosolic viruses and DNA effectively, indicating its crucial role in antiviral defence [8].…”

Section: Cgas-sting Signaling Pathwaymentioning

confidence: 99%

“…1) [8,10,30]. Of note, cGAMP-induced autophagy can clear the cytosolic viruses and DNA effectively, indicating its crucial role in antiviral defence [8]. The ERGIC, which contains cGAMP-bound STING, serves as a membrane source for LC3 recruitment and lipidation.…”

Section: Cgas-sting Signaling Pathwaymentioning

confidence: 99%

“…This process is through a WD repeat domain phosphoinositide-interacting protein 2 (WIPI2) dependent mechanism which is important for LC3 lipidation in the conventional autophagy pathway [31]. LC3-positive membranes target DNA and pathogens to autophagosomes, which are subsequently fused with lysosomes in a process that requires Ras-related protein Rab-7a (RAB7) GTPase [8].…”

Section: Cgas-sting Signaling Pathwaymentioning

confidence: 99%

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STING modulators: Predictive significance in drug discovery

Cui

Zhang

Cen

et al. 2019

European Journal of Medicinal Chemistry

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a b s t r a c tCyclic guanosine monophosphateeadenosine monophosphate synthase (cGAS) d stimulator of interferon genes (STING) signaling pathway plays the critical role in the immune response to DNA. Pharmacological modulation of the STING pathway has been well characterized both from structural and functional perspectives, which paves the way for the drug design of small modulators by medicinal chemists. Here, we outline recent progress in studies on the STING pathway, the structure and biological function of STING, the STING related disease, as well as the rationale and progress in the development of STING modulators. Our review demonstrates that STING is a promising drug target, and providing clues for the discovery of novel STING agonists and antagonists for the potential treatment of various disease including microbial infectious diseases, cancer, and autoimmune disease.

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Endothelial cell autophagy in homeostasis and cancer

et al. 2021

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Autophagy, the major lysosomal pathway for the degradation and recycling of cytoplasmic materials, is increasingly recognized as a major player in endothelial cell (EC) biology and vascular pathology. Particularly in solid tumors, tumor microenvironmental stress such as hypoxia, nutrient deprivation, inflammatory mediators, and metabolic aberrations stimulates autophagy in tumor‐associated blood vessels. Increased autophagy in ECs may serve as a mechanism to alleviate stress and restrict exacerbated inflammatory responses. However, increased autophagy in tumor‐associated ECs can re‐model metabolic pathways and affect the trafficking and surface availability of key mediators and regulators of the interplay between EC and immune cells. In line with this, heightened EC autophagy is involved in pathological angiogenesis, inflammatory, and immune responses. Here, we review major cellular and molecular mechanisms regulated by autophagy in ECs under physiological conditions and discuss recent evidence implicating EC autophagy in tumor angiogenesis and immunosurveillance.

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Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

Cited by 872 publications

References 28 publications

Manipulation of autophagy by (+) RNA viruses

Manipulation of autophagy by (+) RNA viruses

STING modulators: Predictive significance in drug discovery

Endothelial cell autophagy in homeostasis and cancer

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