Ask about this productRelated genes to: TBK1 Blocking Peptide
- Gene:
- TBK1 NIH gene
- Name:
- TANK binding kinase 1
- Previous symbol:
- -
- Synonyms:
- NAK
- Chromosome:
- 12q14.2
- Locus Type:
- gene with protein product
- Date approved:
- 2000-06-08
- Date modifiied:
- 2019-04-23
Related products to: TBK1 Blocking Peptide
Related articles to: TBK1 Blocking Peptide
- Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that is associated with several human malignancies, and primary infection by KSHV can activate both DNA and RNA sensing pathways. Host innate immunity is a rapid, first-line defense against foreign pathogens, where pattern recognition receptors detect virus-associated antigens and activate the type I interferon response to prime the cell to an antiviral state to limit viral infections. However, viruses such as gammaherpesviruses, have evolved mechanisms to co-opt host factors to antagonize these pathways to promote persistent infection. The cellular vaccinia-related kinase (VRK) family is a trio of serine/threonine kinases, VRK1, VRK2 and VRK3, named for their homology to the vaccinia virus B1 kinase. The VRKs are involved in many cellular processes, including nuclear envelope assembly during mitosis and the DNA damage response. However, the role of the VRKs in KSHV infection and innate immunity has not previously been explored. We found that VRK3 is upregulated in response to KSHV primary infection of endothelial cells. VRK3 is also upregulated during KSHV reactivation from latency. Knockdown of VRK3 limited KSHV primary infection and lytic reactivation and resulted in increased activation of TBK1 and IRF3 and subsequent upregulation of interferon stimulated genes. Overexpression of VRK3 reversed this phenotype. Furthermore, we are also the first to demonstrate that VRK3 is a negative regulator of the interferon response even in the absence of viral infection. Collectively, our data highlight the importance of the host factor, VRK3, as a novel suppressor of the type I interferon response during the KSHV viral lifecycle. - Source: PubMed
Publication date: 2026/07/27
Yu Caroline JDamania Blossom - Cellular senescence is accompanied by profound lysosomal alterations, yet whether lysosome-associated factors actively drive aging remains unclear. Through a focused CRISPR/Cas9 screen in human mesenchymal progenitor cells (hMPCs), we identified N-acetylglucosamine-1-phosphotransferase subunits alpha and beta (GNPTAB), an enzyme responsible for lysosomal hydrolase targeting, as a potent regulator of cellular senescence. Genetic ablation of GNPTAB attenuated senescence, whereas its overexpression accelerated senescence. This pro-senescent function occurred independently of GNPTAB's canonical enzymatic role. Instead, GNPTAB binds to the innate immune adaptor stimulator of interferon genes (STING) via a specific interface (E1119), leading to activation of STING and its downstream TANK-binding kinase 1 (TBK1), as well as pro-inflammatory gene expression. A STING-binding-deficient GNPTAB mutant (E1119A) preserved canonical lysosomal functions but failed to induce senescence, while STING depletion abolished GNPTAB-driven senescence. Together, these findings uncover a new signaling pathway wherein GNPTAB engages STING to facilitate its activation, nominating this interface as a potential target for mitigating age-related cellular dysfunction. - Source: PubMed
Publication date: 2026/07/27
Yin JianGao YizhouJing YaobinJiang XiaoyuWang FeiboCai YushengLi Ming-HengCao TianlingWang MinHe YifangZhao HongkaiZhang ShengMa ShuaiWang SiLiu Guang-HuiZhang WeiqiQu Jing - Hypoxic-ischemic encephalopathy (HIE) is a severe perinatal brain injury that often leads to neurological impairments in survivors. Currently, effective therapeutic strategies for HIE remain limited and require further exploration. Emerging evidence indicates that microglia-mediated neuroinflammation plays a pivotal role in the pathophysiology of HIE. Nevertheless, clinically effective anti-inflammatory agents specifically targeting HIE are still lacking. Glycerol-3-phosphate (G3P) is a biologically significant metabolite involved in various cellular metabolic pathways. In this study, we investigated the neuroprotective effects of G3P against hypoxic-ischemic (HI)-induced brain injury by modulating microglial activation. In LPS-treated microglia, G3P suppressed the release of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, reduced reactive oxygen species (ROS) levels, restored mitochondrial membrane potential (MMP), and promoted a shift toward an anti-inflammatory microglial phenotype. In addition, G3P treatment in zebrafish showed no toxicity and significantly mitigated HI-induced oxidative stress, while suppressing both the recruitment and pro-inflammatory activation of mpeg1⁺ macrophages and lyzc⁺ neutrophils. Moreover, administration of G3P dramatically reduced infarct volume and alleviated neuronal loss in rats with hypoxic-ischemic brain damage (HIBD). Y-maze and Morris water maze tests demonstrated that G3P treatment significantly enhanced spatial learning and memory in HIBD rats. Furthermore, G3P markedly reduced the hyperactivation of microglia and astrocytes in both cortical and hippocampal regions. Mechanistically, Immunofluorescence and Western blot analyses revealed that G3P exerted anti-inflammatory effects by inhibiting cyclic GMP-AMP synthase -stimulator of interferon genes (cGAS-STING) signalling pathway and its downstream TBK1/the nuclear factor kappa B (NF-κB) signaling pathway. These findings highlight G3P as a promising therapeutic candidate for HIE. - Source: PubMed
Publication date: 2026/07/25
Qin DaniLei YongLe MeiniCheng MengkeZhao YingminXia LingyunLi XinyuanDong Xiaohua - Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by pruritus and xerosis. Current treatments for AD primarily involve glucocorticoids and immunosuppressive agents. However, long-term administration of these treatments may lead to significant adverse effects. Therefore, there is an urgent need for effective therapeutic alternatives with improved safety profiles. (Burkill) F. H. Chen is renowned for its diverse pharmacological properties and shows promise in the treatment of skin diseases. - Source: PubMed
Publication date: 2026/07/09
Zhu XuWang YichunChen ZhongyiZhao ZiyanYang ChunhaoXu PengQu LipingWang FeifeiXiao Fengkun - The CGAS-STING1 pathway is an innate immune system that can detect double-stranded DNA in the cytoplasm and trigger antiviral immune responses. Increasing evidence indicates that CGAS-STING1 signaling can induce autophagy; however, the activation and potential role of the CGAS-STING1-dependent autophagy during RNA virus infection remain unclear. Here, we initially observed that cytosolic DNA acts as a potent inducer of CGAS-STING1-dependent autophagy. Unexpectedly, pre-activation of this pathway via DNA-CGAS-STING1 (1-340) transfection significantly promoted the replication of RNA viruses tested including SFTSV and enterovirus 71 (EV-71). Using SFTSV as a model to investigate the physiological trigger during infection, we demonstrated that SFTSV induces mitochondrial damage, leading to the leakage of mitochondrial DNA (mtDNA) into the cytoplasm. This endogenous mtDNA activates CGAS-STING1-dependent autophagy, which SFTSV then exploits for its replication. Indeed, depletion of mtDNA abolishes SFTSV-induced autophagy and impairs viral replication. Mechanistically, the SFTSV nucleoprotein directly interacts with STING1, hijacking STING1-derived membranes from the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi apparatus to form its replication platform. Our study reveals a new host anti-RNA virus strategy, namely activating CGAS-STING1-dependent autophagy through cytosolic DNA, as well as the mechanism by which SFTSV hijacks CGAS-STING1-dependent autophagy for viral replication.: CGAS: cyclic GMP-AMP synthase; ER: endoplasmic reticulum; ERGIC: endoplasmic reticulum-Golgi intermediate compartment; EV-71: enterovirus 71; EtBr: ethidium bromide; Gn: glycoproteins N; IFN-I: type I interferon; KO: knockout; MOIs: multiplicities of infection; NP: nucleoprotein; NSs: non-structural proteins; ROS: reactive oxygen species; SFTSV: Severe fever with thrombocytopenia syndrome virus; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; VDAC1: voltage dependent anion channel 1; WT: wild-type; gDNA: genomic DNA; mtDNA: mitochondrial DNA. - Source: PubMed
Publication date: 2026/07/23
Gu Xiao-LanLiu QiaoZhang Wen-KangLi BangYan Li-NaYu Xue-Jie