Advances in the prerequisite and consequence of STING downstream signalosomes

Abstract: 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 secondary messenger 2′3′-cyclic GMP-AMP (cGAMP) is produced by cGAS and in turn activates its adapter STING in the endoplasmic reticulum (ER). Resting-state or activated STING protein is finely restricted by multiple degradation machineries. 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-I and 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 inflammasome, 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 surveillance 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 implications for new approaches in hunt for the next generation of cancer immunotherapy base on STING.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Advances in the prerequisite and consequence of STING downstream signalosomes ; volume:4 ; number:5 ; year:2024 ; pages:435-451 ; extent:17 ; Medical Review ; 4, Heft 5 (2024), 435-451 (gesamt 17)

Contributors, Places and Time

• Creator: Lu, Xinliang ; Li, Xiaobing ; Li, Lili ; Han, Chuanhui ; Li, Sirui

Further information

• DOI: 10.1515/mr-2024-0016
• URN: urn:nbn:de:101:1-2410231535128.119214031700
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:33 AM CEST