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Adaptor protein 1

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https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#1
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein - apoptosis associated speck-like protein containing a caspase-activation and -recruitment domain (ASC) - activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 20, 2017: International Immunology
https://www.readbyqxmd.com/read/28529112/myeloid-differentiation-factor-88-is-up-regulated-in-epileptic-brain-and-contributes-to-experimental-seizures-in-rats
#2
Na Wang, Xiong Han, Haipeng Liu, Ting Zhao, Jie Li, Yan Feng, Xiujuan Mi, Yanke Zhang, Yanan Chen, Xuefeng Wang
Accumulating evidence supports that activation of inflammatory pathways is a crucial factor contributing to the pathogenesis of seizures. In particular, the activation of interleukin-1 beta (IL-1β) system exerts proconvulsant effects in a large variety of seizure models. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein in the signaling cascade elicited by IL-1β. The present study aimed to investigate the expression pattern of MyD88 in rat models of seizures and in patients with refractory temporal lobe epilepsy (TLE), and to study the role of MyD88 in epileptic seizures...
May 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28528692/insulin-like-growth-factor-igf-axis-in-cancerogenesis
#3
REVIEW
Aldona Kasprzak, Wojciech Kwasniewski, Agnieszka Adamek, Anna Gozdzicka-Jozefiak
Determination of the role of insulin-like growth factor (IGF) family components in carcinogenesis of several human tumors is based on numerous epidemiological and pre-clinical studies, experiments in vivo and in vitro and on attempts at application of drugs affecting the IGF axis. Investigative hypotheses in original studies were based on biological functions manifested by the entire family of IGF (ligands, receptors, linking proteins, adaptor molecules). In the context of carcinogenesis the most important functions of IGF family involve intensification of proliferation and inhibition of cell apoptosis and effect on cell transformation through synthesis of several regulatory proteins...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28528205/heterotrimeric-complex-of-p38-mapk-pkc%C3%AE-and-tirap-is-required-for-ap1-mediated-inflammatory-response
#4
Mirza S Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes...
May 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28527629/p62-sequestosome-1-knockout-delays-neurodegeneration-induced-by-drp1-loss
#5
Tatsuya Yamada, Yoshihiro Adachi, Toru Yanagawa, Miho Iijima, Hiromi Sesaki
Purkinje neurons, one of the largest neurons in the brain, are critical for controlling body movements, and the dysfunction and degeneration of these cells cause ataxia. Purkinje neurons require a very efficient energy supply from mitochondria because of their large size and extensive dendritic arbors. We have previously shown that mitochondrial division mediated by dynamin-related protein 1 (Drp1) is critical for the development and survival of Purkinje neurons. Drp1 deficiency has been associated with one of the major types of ataxia: autosomal recessive spastic ataxia of Charlevoix Saguenay...
May 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28526927/sodium-thiosulphate-attenuates-brain-inflammation-induced-by-systemic-lipopolysaccharide-administration-in-c57bl-6j-mice
#6
Gonzalo Acero, Miryam Nava Catorce, Ricardo González-Mendoza, Marco Antonio Meraz-Rodríguez, Luis Fernando Hernández-Zimbron, Roberto González-Salinas, Goar Gevorkian
It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration...
May 19, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28526413/tcr-crosslinking-promotes-crk-adaptor-protein-binding-to-tyrosine-phosphorylated-cd3%C3%AE-chain
#7
Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Sigal Gelkop, Noah Isakov
T cell antigen receptor (TCR) binding of a peptide antigen presented by antigen-presenting cells (APCs) in the context of surface MHC molecules initiates signaling events that regulate T cell activation, proliferation and differentiation. A key event in the activation process is the phosphorylation of the conserved tyrosine residues within the CD3 chain immunoreceptor tyrosine-based activation motifs (ITAMs), which operate as docking sites for SH2 domain-containing effector proteins. Phosphorylation of the CD3ζ ITAMs renders the CD3 chain capable of binding the ζ-chain associated protein 70 kDa (ZAP70), a protein tyrosine kinase that is essential for T cell activation...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28522851/mouse-rif1-is-a-regulatory-subunit-of-protein-phosphatase-1-pp1
#8
Rasa Sukackaite, Daniela Cornacchia, Malene Ringkjøbing Jensen, Philippe J Mas, Martin Blackledge, Elin Enervald, Guangyou Duan, Tania Auchynnikava, Maja Köhn, Darren J Hart, Sara B C Buonomo
Rif1 is a conserved protein that plays essential roles in orchestrating DNA replication timing, controlling nuclear architecture, telomere length and DNA repair. However, the relationship between these different roles, as well as the molecular basis of Rif1 function is still unclear. The association of Rif1 with insoluble nuclear lamina has thus far hampered exhaustive characterization of the associated protein complexes. We devised a protocol that overcomes this problem, and were thus able to discover a number of novel Rif1 interactors, involved in chromatin metabolism and phosphorylation...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28516117/reconstruction-of-the-mouse-inflammasome-system-in-hek293t-cells
#9
Hexin Shi, Anne Murray, Bruce Beutler
The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and the protein kinase NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et al., 2016). When cells are exposed to microbes and/or danger signals, the inflammasome assembles and serves as a platform for the activation of caspase-1. Caspase-1 activation promotes the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-33 as well as pyroptosis induction (Gross et al...
November 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28512249/p62-sqstm1-cooperates-with-hyperactive-mtorc1-to-regulate-glutathione-production-maintain-mitochondrial-integrity-and-promote-tumorigenesis
#10
Hilaire C Lam, Christian V Baglini, Alicia Llorente Lope, Andrey Parkhitko, Heng-Jia Liu, Nicola Alesi, Izabela A Malinowska, Darius Ebrahimi-Fakhari, Afshin Saffari, Jane J Yu, Ana Pereira, Damir Khabibullin, Barbara Ogorek, Julie S Nijmeh, Taylor Kavanagh, Adam Handen, Stephen Y Chan, John M Asara, William M Oldham, Maria Diaz-Meco, Jorge Moscat, Mustafa Sahin, Carmen Priolo, Elizabeth P Henske
p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic substrate which accumulates in cells with hyperactive mTORC1, such as kidney cells with mutations in the tumor suppressor genes TSC1 or TSC2. Here we report that p62 is a critical mediator of TSC2-driven tumorigenesis, as Tsc2+/- and Tsc2f/f Ksp-CreERT2+ mice crossed to p62-/- mice were protected from renal tumor development. Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH)...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511952/lithium-ameliorates-lipopolysaccharide-induced-neurotoxicity-in-the-cortex-and-hippocampus-of-the-adult-rat-brain
#11
Muhammad Sohail Khan, Tahir Ali, Muhammad Noman Abid, Myeung Hoon Jo, Amjad Khan, Min Woo Kim, Gwang Ho Yoon, Eun Woo Cheon, Shafiq Ur Rehman, Myeong Ok Kim
Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor-kB (NF-KB) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α)...
May 13, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28506384/managing-the-challenging-homozygous-familial-hypercholesterolemia-patient-academic-insights-and-practical-approaches-for-a-severe-dyslipidemia-a-national-lipid-association-masters-summit
#12
EDITORIAL
G Kees Hovingh, Anne C Goldberg, Patrick M Moriarty
The following article represents material presented and discussed at a symposium hosted by the National Lipid Association hosted entitled "Managing the Challenging Homozygous Familial Hypercholesterolemia Patient-Academic Insights and Practical Approaches for a Severe Dyslipidemia" on November 7, 2015 in Orlando, FL. Presenters included G.K.H., A.C.G, and P.M.M. The diagnosis and genetic causes of extremely high low-density lipoprotein (LDL) cholesterol, which has become known as homozygous familial hypercholesterolemia, were discussed...
May 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28504462/endocytic-activity-of-hiv-1-vpu-phosphoserine-dependent-interactions-with-clathrin-adaptors
#13
Charlotte A Stoneham, Rajendra Singh, Xiaofei Jia, Yong Xiong, John Guatelli
HIV-1 Vpu modulates cellular transmembrane proteins to optimize viral replication and provide immune-evasion, triggering ubiquitin-mediated degradation of some targets but also modulating endosomal trafficking to deplete them from the plasma membrane. Interactions between Vpu and the heterotetrameric clathrin adaptors AP-1 and AP-2 have been described, yet the molecular basis and functional roles of such interactions are incompletely defined. To investigate the trafficking signals encoded by Vpu, we fused the cytoplasmic domain (CD) of Vpu to the extracellular and transmembrane domains of the CD8 α-chain...
May 14, 2017: Traffic
https://www.readbyqxmd.com/read/28502093/the-tlr4-trif-pathway-can-protect-against-the-development-of-experimental-allergic-asthma
#14
Karim H Shalaby, Saba Al-Heialy, Kimitake Tsuchiya, Soroor Farahnak, Toby K McGovern, Paul-Andre Risse, Woong-Kyung Suh, Salman T Qureshi, James G Martin
The Toll-like Receptor (TLR) adaptor proteins Myeloid Differentiating Factor 88 (MyD88) and Toll, interleukin-1 Receptor and Resistance protein (TIR) domain-containing adaptor inducing interferon-β (TRIF) comprise the two principal limbs of the TLR signaling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4+ICOS+ T cells by nasal application of Protollin(™) , a mucosal adjuvant composed of TLR2 and 4 agonists. Wild-type (wt), Trif -/- or Myd88 -/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges...
May 14, 2017: Immunology
https://www.readbyqxmd.com/read/28501563/kindlin-1-protects-cells-from-oxidative-damage-through-activation-of-erk-signalling
#15
Hila Emmert, Hitesh Patel, Valerie G Brunton
Kindlin-1 is a FERM domain containing adaptor protein that is found predominantly at cell-extracellular matrix adhesions where it binds to β-integrin subunits and is required for integrin activation. Loss of function mutations in the FERMT1 gene which encodes Kindlin-1 leads to the development of Kindler Syndrome (KS) an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, and predisposition to aggressive squamous cell carcinoma (SCC). Here we show that loss of Kindlin-1 sensitizes both SCC cells and keratinocytes to oxidative stress: Kindlin-1 deficient cells have higher levels of reactive oxygen species, decreased viability and increased DNA damage after treatment with either hydrogen peroxide (H2O2) or irradiation with UVA...
May 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28494724/c-type-lectin-receptor-old-friend-and-new-player
#16
Hai Hou, Yahui Guo, Qing Chang, Tianming Luo, Xin Wu, Xueqiang Zhao
During the last two decades, C-type lectin receptors (CLRs) have been demonstrated to play key roles in initiating the host immune response upon fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2, Dectin-3 and Mincle, recognize the cell wall component from the infected microorganisms by using their carbohydrate recognition domain (CRD). Upon stimulation, CLRs induce multiple signal transduction cascades through their own immune-receptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ, which then lead to the activation of nuclear factor kappa B (NF-kB) through Syk- and CARD9-dependent pathway...
May 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28484272/effect-of-bacillus-subtilis-on-aeromonas-hydrophila-induced-intestinal-mucosal-barrier-function-damage-and-inflammation-in-grass-carp-ctenopharyngodon-idella
#17
Weiguang Kong, Can Huang, Ying Tang, Ding Zhang, Zhixin Wu, Xiaoxuan Chen
Our study explored the effect of oral intubation of Bacillus subtilis on Aeromonas hydrophila-induced intestinal mucosal barrier function damage and inflammation in grass carp. The mid-intestine mucosal tissue was collected for ATPase activity measurement. Intestinal mucosa was also ultrastructurally examined with transmission electron microscope (TEM), and its permeability was determined using Evans blue (EB) and D-lactic acid. The mid-intestine pro-inflammation cytokine, MyD88 and tight junction (TJ) protein mRNA expression levels were measured using real-time quantitative PCR...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484055/endothelial-cd2ap-binds-the-receptor-icam-1-to-control-mechanosignaling-leukocyte-adhesion-and-the-route-of-leukocyte-diapedesis-in-vitro
#18
Antje Schaefer, Trynette J van Duijn, Jisca Majolee, Keith Burridge, Peter L Hordijk
Inflammation is driven by excessive transmigration (diapedesis) of leukocytes from the blood to the tissue across the endothelial cell monolayer that lines blood vessels. Leukocyte adhesion, crawling, and transmigration are regulated by clustering of the endothelial mechanosensitive receptor intercellular adhesion molecule-1 (ICAM-1). Whereas several proteins are known to promote ICAM-1 function, the molecular mechanisms that limit ICAM-1-mediated adhesion to prevent excessive leukocyte transmigration remain unknown...
May 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28483816/a-pseudomonas-aeruginosa%C3%A2-tir-effector-mediates-immune-evasion-by-targeting%C3%A2-ubap1-and-tlr-adaptors
#19
Paul Rc Imbert, Arthur Louche, Jean-Baptiste Luizet, Teddy Grandjean, Sarah Bigot, Thomas E Wood, Stéphanie Gagné, Amandine Blanco, Lydia Wunderley, Laurent Terradot, Philip Woodman, Steve Garvis, Alain Filloux, Benoit Guery, Suzana P Salcedo
Bacterial pathogens often subvert the innate immune system to establish a successful infection. The direct inhibition of downstream components of innate immune pathways is particularly well documented but how bacteria interfere with receptor proximal events is far less well understood. Here, we describe a Toll/interleukin 1 receptor (TIR) domain-containing protein (PumA) of the multi-drug resistant Pseudomonas aeruginosa PA7 strain. We found that PumA is essential for virulence and inhibits NF-κB, a property transferable to non-PumA strain PA14, suggesting no additional factors are needed for PumA function...
May 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28480979/down-regulation-of-trif-tlr3-and-mavs-in-hcv-infected-liver-correlates-with-the-outcome-of-infection
#20
Premashis Kar, Deepak Kumar, Phani Kumar Gumma, Soumya Jyoti Chowdhury, Vijay Kumar Karra
AIMS: In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-β (TRIF) and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-κB) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF and TRAF6 outcome of HCV infection...
May 8, 2017: Journal of Medical Virology
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