Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/anie.202300978 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Grass carp reovirus VP4 manipulates TOLLIP to degrade STING for inhibition of IFN production.
J Virol
January 2025
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Unlabelled: Although fish possess an effective interferon (IFN) system to defend against viral infection, grass carp reovirus (GCRV) still causes epidemic hemorrhagic disease and tremendous economic loss in grass carp. Therefore, it is necessary to investigate the immune escape strategies employed by GCRV. In this study, we show that the structural protein VP4 of GCRV (encoded by the S6 segment) significantly restricts IFN expression by degrading stimulator of IFN genes (STING) through the autophagy-lysosome-dependent pathway.
View Article and Find Full Text PDFCapnocytophaga canimorsus in Iliac Artery Mycotic Aneurysm: The Role of Molecular Diagnostics.
Am J Case Rep
January 2025
Vascular and Endovascular Surgery, Department of Cardiovascular Surgery, Mayo Clinic Health System, Eau Claire, WI, USA.
BACKGROUND The bacterial organism Capnocytophaga canimorsus is an oral commensal of cats and dogs and can cause life-threatening infections like mycotic aneurysm, meningitis, and sepsis. Mycotic aneurysms occur when microbial infections cause arterial wall degeneration. Difficulty in diagnosing Capnocytophaga canimorsus infection can occur due to the bacteria's fastidious nature and laboratory testing limitations, contributing to the infection's high morbidity and mortality.
View Article and Find Full Text PDFMapping evidence on the regulations affecting accessibility, availability and management of snake antivenom globally: a scoping review protocol.
BMJ Open
December 2024
Department of Pharmacology, University of Pretoria, Pretoria, South Africa.
Introduction: Snakebite envenomation has been declared a neglected tropical disease by the WHO since 2017. The disease is endemic in affected areas due to the lack of availability and access to antivenom, despite it being the standard treatment for snakebites. This challenge is perpetuated by the shortcomings of the regulatory systems and policies governing the management of antivenoms.
View Article and Find Full Text PDFRole of AIM2 and cGAS-STING signaling in high fat high carbohydrate diet-induced gut dysbiosis associated neurodegeneration.
Life Sci
January 2025
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research, Chunilal Bhawan, 168, Maniktala Main Rd, Kolkata, West Bengal 700054, India. Electronic address:
Aims: Gut dysbiosis modulates CNS complications and cognitive decline through the gut-brain axis. The study aims to investigate the molecular mechanisms involved in gut dysbiosis-associated cognitive changes and the potential effects of probiotics in high fat-high carbohydrate diet-induced gut dysbiosis-associated neurodegeneration.
Materials And Methods: We used high fat, high-carbohydrate diet (HFHCD) and high-fat diet (HFD) to induce gut dysbiosis-associated neurodegeneration in C57BL/6 mice.
Liver-Secreted Extracellular Vesicles Promote Cirrhosis-Associated Skeletal Muscle Injury Through mtDNA-cGAS/STING Axis.
Adv Sci (Weinh)
January 2025
Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, 610041, China.
Skeletal muscle atrophy (sarcopenia) is a serious complication of liver cirrhosis, and chronic muscle inflammation plays a pivotal role in its pathologenesis. However, the detailed mechanism through which injured liver tissues mediate skeletal muscle inflammatory injury remains elusive. Here, it is reported that injured hepatocytes might secrete mtDNA-enriched extracellular vesicles (EVs) to trigger skeletal muscle inflammation by activating the cGAS-STING pathway.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!