DOI: 10.1515/mr-2024-0016
Advances in the prerequisite and consequence of STING downstream signalosomes
Xinliang Lu1
Xiaobing Li2
Lili Li3
Chuanhui Han4
Sirui Li5
1.Institute of Immunology and Bone Marrow Transplantation Center of the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China2.InvivoGen Ltd.,Hong Kong Science and Technology Parks,Hong Kong,China3.Center for Systems Medicine,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China;Suzhou Institute of Systems Medicine,Suzhou,Jiangsu,China4.Peking University International Cancer Institute,Peking University Cancer Hospital and Institute,Health Science Center,Peking University,Beijing,100084,China5.Lineberger Comprehensive Cancer Center,University of North Carolina at Chapel Hill,Chapel Hill,NC 27599,USA
摘要：The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)pathway is an evolving DNA-sensing mechanism involved in innate immunity and pathogen defense that has been optimized while remaining conserved.Aside from recognizing pathogens through conserved motifs,these receptors also detect aberrant or misplaced self-molecules as possible signs of perturbed homeostasis.Upon binding external or self-derived DNA,a mobile sec-ondary messenger 2'3'-cyclic GMP-AMP(cGAMP)is produced by cGAS and in turn activates its adapter STING in the endo-plasmic reticulum(ER).Resting-state or activated STING protein is finely restricted by multiple degradation machin-eries.The post-translational changes of the STING protein,along with the regulatory machinery of the secret routes,limit the onset,strength and sustention of STING signal.STING experiences a conformational shift and relocates with TBK1 from the ER to perinuclear vesicles containing transcription factors,provoking the transcription activity of IRF3/IFN-Ⅰand NF-κB pathways,as well as to initiate a number of cellular processes that have been shown to alter the immune landscape in cancer,such as autophagy,NLRP3 inflamma-some,ER stress,and cell death.STING signal thus serves as a potent activator for immune mobilization yet also triggers immune-mediated pathology in tissues.Recent advances have established the vital role of STING in immune surveil-lance as well as tumorigenic process.This review provides an overview of the disparate outcomes of cancer attributed to the actions of pleiotropic and coordinated STING downstream signalosomes,along with the underlying mechanisms of STING function in pathologies,providing therapeutic impli-cations for new approaches in hunt for the next generation of cancer immunotherapy base on STING.
机标关键词：stingadvancesconsequencedownstreamprerequisitesignalosomes
论文发表日期：2024-10-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：17( 435-451 )
英文信息