TANK-binding kinase 1 (TBK1) is a serine/threonine kinase with well-established roles as a central player in innate immune signaling. Dysregulation of TBK1 activity has been implicated in a variety of pathophysiologic conditions, including cancer. Generally, TBK1 acts as an oncogene and increased TBK1 activity, indicated by increased phosphorylation at the Ser172 residue, can be observed in multiple human cancers. TBK1 can be activated either by autophosphorylation of Ser172 or transphosphorylation at this site by upstream kinases. Serving as a hub for integrating numerous extracellular and intracellular signals, TBK1 can be activated through multiple signaling pathways. However, the direct upstream kinase responsible for TBK1 activation remains elusive, which limits our comprehensive understanding of its activation mechanism and potential therapeutic application targeting TBK1-related signaling especially in cancer. In this review, we summarize the findings on mechanisms of TBK1 activation in cancer cells and recent discoveries that shed light on the direct upstream kinases promoting TBK1 activation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402294 | PMC |
| http://dx.doi.org/10.1016/j.cellin.2024.100197 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease.
Cell Rep
December 2024
School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel; Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. Electronic address:
Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples.
View Article and Find Full Text PDFDl-3-n-butylphthalide Alleviates Cardiac Dysfunction and Injury Possibly by Inhibiting Cell Pyroptosis and Inflammation via the cGAS-STING-TBK1 Pathway in a Porcine Model of Hemorrhage-Induced Cardiac Arrest.
Shock
December 2024
Department of Emergency Medicine, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
Introduction: Dl-3-n-butylphthalide (NBP), a small molecular compound extracted from celery seeds, has been shown to exhibit diverse pharmacological activities, including anti-inflammatory, antioxidative, and anti-apoptotic effects. Recent studies have highlighted its efficacy in treating various cardiovascular conditions, such as myocardial infarction, hypertrophy, heart failure, and cardiotoxicity. This study aimed to investigate whether NBP could alleviate cardiac dysfunction and injury following hemorrhage-induced cardiac arrest (HCA) in a porcine model and elucidate its potential mechanisms.
View Article and Find Full Text PDFLinear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.
Autophagy
January 2025
Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.
View Article and Find Full Text PDFTBK1 inhibitor amlexanox exerts anti-cancer effects against endometrial cancer by regulating AKT/NF-κB signaling.
Int J Biol Sci
January 2025
Department of Cell Biology, Konyang University College of Medicine, Daejeon 35365, Republic of Korea.
Article Synopsis
- Endometrial cancer is a serious gynecological issue, and the study focused on the role of TBK1, a kinase involved in inflammation and immunity, in this cancer type.
- Research found that low TBK1 expression is linked to better patient outcomes, and inhibiting TBK1 with amlexanox reduced cancer cell growth and migration.
- The effects of amlexanox were shown to work through the AKT/NF-κB signaling pathway, suggesting a new direction for cancer treatments targeting TBK1 in endometrial cancer.
DHAV-1 3C protein promotes viral proliferation by antagonizing type I interferon via upregulating the ANXA2 protein.
Int J Biol Macromol
December 2024
Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China.; College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Chengdu 611130, China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China.
The picornavirus 3C protein plays a crucial role in viral infection. One of its functions is inhibiting the immune response by cleaving or degrading innate immune-related proteins to promote viral infection. Annexin A2 (ANXA2) is a multifunctional host protein that plays a key role in various cellular processes, it also participates in viral infection.
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!