Conference Article| February 01 1996 Investigation into the role of protein kinase C in IL1 and PMA signalling in EL4.NOB-1 thymoma cells T. M. Mahon; T. M. Mahon 1Department of Biochemistry and Biotechnology Institute, Trinity College Dublin, Ireland Search for other works by this author on: This Site PubMed Google Scholar L. A. J. O'neill L. A. J. O'neill 1Department of Biochemistry and Biotechnology Institute, Trinity College Dublin, Ireland Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1996 Biochemical Society1996 Biochem Soc Trans (1996) 24 (1): 81S. https://doi.org/10.1042/bst024081s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation T. M. Mahon, L. A. J. O'neill; Investigation into the role of protein kinase C in IL1 and PMA signalling in EL4.NOB-1 thymoma cells. Biochem Soc Trans 1 February 1996; 24 (1): 81S. doi: https://doi.org/10.1042/bst024081s Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: Interleukin-1: IL1, Phorbol myristate acetate: PMA This content is only available as a PDF. © 1996 Biochemical Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.
Toll-like receptors (TLRs) are key components of the innate immune system, functioning as pattern recognition receptors that recognise a wide range of microbial pathogens. TLRs represent a primary line of defence against invading pathogens in mammals, plants and insects. Recognition of microbial components by TLRs triggers a cascade of cellular signals that culminates in the activation of NFκB which leads to inflammatory gene expression and clearance of the infectious agent. The history of NFκB began with the TLR4 ligand lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, since this was the stimulus first used to activate NFκB in pre-B-cells. However, since those early days it has been a circuitous route, made possible by drawing on information provided by many different fields, that has led us not only to the discovery of TLRs but also to an understanding of the complex pathways that lead from TLR ligation to NFκB activation. In this review we will summarize the current knowledge of TLR-mediated NFκB activation, and also the recent discoveries that subtle differences in κB binding sequences and NFκB dimer formation result in specific gene expression profiles.
The nuclear factor (NF)-κB family of transcription factors is a key participant in multiple biological processes, most notably in the immune and inflammatory response. Five proteins make up the NF-κB family, and these proteins can hetero- and homo-dimerize, giving rise to diversity. Recently, it has been shown that certain members can also interact directly with other transcription factors such as signal transducers of activated transcription, interferon regulatory factor family members and p53, providing further diversity. We propose that this promiscuity might help explain the many of roles of NF-κB in specialized cell function and fate. Furthermore, the state of a cell and its cellular background in addition to overall promoter structure and variations in the κB target sequence will all define the composition and activity of multimeric NF-κB complexes.
No abstract is provided for this article.
A major question remaining in the field of evolutionary biology is how prokaryotic organisms made the leap to complex eukaryotic life. The prevailing theory depicts the origin of eukaryotic cell complexity as emerging from the symbiosis between an α-proteobacterium, the ancestor of present-day mitochondria, and an archaeal host (endosymbiont theory). A primary contribution of mitochondria to eukaryogenesis has been attributed to the mitochondrial genome, which enabled the successful internalisation of bioenergetic membranes and facilitated remarkable genome expansion. It has also been postulated that a key contribution of the archaeal host during eukaryogenesis was in providing ‘archaeal histones’ that would enable compaction and regulation of an expanded genome. Yet, how the communication between the host and the symbiont evolved is unclear. Here, we propose an evolutionary concept in which mitochondrial TCA cycle signalling was also a crucial player during eukaryogenesis enabling the dynamic control of an expanded genome via regulation of DNA and histone modifications. Furthermore, we discuss how TCA cycle remodelling is a common evolutionary strategy invoked by eukaryotic organisms to coordinate stress responses and gene expression programmes, with a particular focus on the TCA cycle-derived metabolite itaconate.
When immune cells are activated, they undergo metabolic change in order to have sufficient energy to function effectively. The Krebs cycle is one of the most important pathways involved in this response and citrate, a critical component of this pathway, regulates carbohydrate and lipid metabolism.
York et al. identify a role for decreased cholesterol biosynthesis in virally infected cells as a critical event in the induction of the anti-viral response. The mechanism involves enhanced signaling by STING in the ER membrane in response to the second messenger cGAMP, promoting increased transcription of type I interferons. The authors suggest that a “lipid code” is being sensed by STING to allow it to signal.
No abstract is provided for this article.
No abstract is provided for this article.
Toll-like receptors (TLRs) in the host recognize conserved microbial products and defend against pathogenic attack by initiating an immune response via signalling pathways that lead to an increase in immune and inflammatory gene expression. TLR signalling must be stringently regulated in order to ensure sufficient clearance of pathogens and a timely return to homeostasis after infection. MicroRNAs (miRNAs) are a newly discovered class of gene regulators which bind to the 3′ untranslated region of target mRNA and direct their post-transcriptional repression. They are global regulators potentially controlling up to 30% of the human genome. Several miRNAs have been shown to be up-regulated in response to TLR ligands, and many directly target components of the TLR signalling system, revealing a whole extra level of control of TLR signalling which is being extensively researched. The dysregulation of miRNAs may be involved in many inflammatory diseases and cancers and thus merits further investigation. In this review, we focus in on a trio of miRNA which have proven to be key in many immune and inflammatory pathways; miR-155, miR-21 and miR-146.
