China
Africa
Explore chapters and articles related to this topic
Nuclear Factor Kappa-B: Bridging Inflammation and Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Mohammad Aslam Khan, Girijesh Kumar Patel, Haseeb Zubair, Nikhil Tyagi, Shafquat Azim, Seema Singh, Aamir Ahmad, Ajay Pratap Singh
Several regulatory mechanisms and crosstalks have been proposed for the non-canonical pathway of NF-κB activation. During stimulation, IKKα exhibits negative feedback mechanism and destabilizes NIK levels while another kinase, TANK-binding kinase1 (TBK1), also phosphorylates and controls stability of NIK in a signal-dependent manner [74, 75]. De-ubiquitinase, OTU deubiquitinase 7B (OTUD7b), acts as negative regulator for the activation of non-canonical NF-κB pathway. After binding to TRAF3, OUTD7b deubiquitinates TRAF3 and indirectly controls the levels of NIK in a signal-dependent manner [76].
Degenerative Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James A. Mastrianni, Elizabeth A. Harris
Up to 25% of FTD cases appear to have an autosomal dominant inheritance pattern; however, 20–40% show instead a polygenic familial inheritance pattern. Mutations in the following genes are associated with familial FTDs:15–19MAPτ on chromosome 17q21–22, encoding tau protein.GRN on chromosome 17q21.32, encoding progranulin.C9orf72 on the short arm of chromosome 9, noncoding.VCP, CHMP2B, TBK1, FUS, and TARDBP (less commonly).
CBL Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The MAPK pathway includes two major components: the RAS gene family and the MAPK pathway, which contains RAF, one of the major downstream RAS effectors (the others being PI3K and RAL–GEF, forming part of the PI3K/AKT/mTOR pathway and the Ral-GEF/TBK1/IRF3/3-NF-κB pathway, respectively). As a ubiquitous, highly conserved intracellular signaling network, the RAS/MAPK signaling pathway participates in cell cycle regulation, differentiation, growth, apoptosis, and senescence.
Low STING expression promotes endometrial stromal cell invasion and migration via the STING/IRF-3/IFN-β1 pathway in eutopic endometrium of women with endometriosis
Published in Gynecological Endocrinology, 2022
Zhen Xu, Heng Zhao, Caixin Yue, Lixia Zhang, Muzi Li, ,Yanbo Du, ,Na Zhang, Lei Yan
The imbalanced innate immune response is responsible for endometriosis onset and progression. STING plays important role in innate immunity; as a DNA receptor, STING can recognize released cellular DNA. Accordingly, endogenous molecules released during endometriosis as a result of tissue damage or inflammatory response, such as HMGB1 and IL-33, can activate STING signaling pathway [18,30,31]. Innate immune system activation initiates the signaling mediated by TBK1 and its downstream transcription regulator IRF3, eventually resulting in type I interferon production. Transmembrane STING acts as one of the key cellular DNA receptor that can recognize released DNA and activate TBK1 of the IRF3 signaling pathway to release type I interferons. In our study, STING expression decreased in eutopic endometrial tissues of women with endometriosis, whereas the proliferation, invasion, and migration of endometrial stromal cells increased. Based on these results, we postulate that STING may exert anti-tumor effects in endometriosis, which help to prevent ectopic lesion formation. We also observed altered STING signaling pathway in endometrial stromal cells. Moreover, exogenous addition of IFN-β1 reduced the invasion and migration of stromal cells, confirming that STING may have a similar role in tumor immunotherapy and could be a potential target for endometriosis treatment.
Targeting TANK-binding kinase 1 (TBK1) in cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Or-Yam Revach, Shuming Liu, Russell W. Jenkins
In addition to its well-established role in coordinating innate immune signaling, additional roles for TBK1 have been described, including regulation of inflammation, autophagy, cell cycle, cell death, and metabolism. Dysregulated TBK1 signaling has been implicated in several human disease states, although there has been an increasing interest in the role of TBK1 in cancer pathogenesis [5–10]. Despite the growing interest in studying the role(s) and regulation of TBK1 in cancer, the precise molecular mechanisms governing TBK1 signaling and its subsequent impact on cancer biology remain incompletely understood. In this article, we will review the structure and function of TBK1, including its cellular roles, mechanisms of regulation, role in cancer pathogenesis, and therapeutic targeting in cancer. We searched pubmed.ncbi.nlm.nih.gov for the following search terms with various combinations: TBK1, IKK, inhibitors, cancer, tumor microenvironment. We reviewed relevant papers from 1999 to 2020.
TANK-binding kinase 1 as a novel therapeutic target for viral diseases
Published in Expert Opinion on Therapeutic Targets, 2019
Innate immunity is the first line of the host to defend against invading viruses. During viral infection, the activation and expression of antiviral signaling adaptors as the ‘strategic military area’ to fight for survival by both host and invading viruses [18]. TBK1 is a key kinase involved in antiviral innate immunity, and its activity is crucial for the host to battle with viruses. In addition, multiple viruses have evolved a variety of strategies to facilitate their immune escape by manipulating TBK1 activity. In light of its fundamental roles in antiviral responses, TBK1 will be a vital therapeutic target in viral diseases. In this review, we put emphasis on the regulation of TBK1, in order to throw light on the important therapeutic target with applications in viral diseases.