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https://www.readbyqxmd.com/read/28534516/transcriptional-and-posttranscriptional-regulation-of-hoxa13-by-lncrna-hottip-facilitates-tumorigenesis-and-metastasis-in-esophageal-squamous-carcinoma-cells
#1
C Lin, Y Wang, Y Wang, S Zhang, L Yu, C Guo, H Xu
The long non-coding RNA, HOTTIP, has an important role in tumorigenesis. It is known that HOTTIP regulates HOX gene family; however, its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. In this study, we investigated the role of HOTTIP in ESCC and observed that HOTTIP/HOXA13 was upregulated in ESCC and promoted cell proliferation and metastasis in vivo and in vitro. Interestingly, harboring a miR-30b-binding site, HOTTIP as a molecular sponge mainly regulated miR-30b level in the nucleus and modulated the repression of HOXA13 mediated by miR-30b in the cytoplasm, resulting in the positive HOTTIP/HOXA13 correlation...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533472/yersinia-pestis-yopk-inhibits-bacterial-adhesion-to-host-cells-by-binding-to-the-extracellular-matrix-adaptor-protein-matrilin-2
#2
Yafang Tan, Wanbing Liu, Qingwen Zhang, Shiyang Cao, Haihong Zhao, Tong Wang, Zhizhen Qi, Yanping Han, Yajun Song, Xiaoyi Wang, Ruifu Yang, Zongmin Du
Pathogenic yersiniae harbor a type III secretion system (T3SS) that injects Yersinia outer protein (Yop) into host cells. YopK has been shown to control Yop translocation and prevent inflammasome recognition of T3SS by the innate immune system. Here, we demonstrate that YopK inhibits bacterial adherence to host cells by binding to the extracellular matrix adaptor protein matrilin-2 (MATN2). YopK binds to MATN2 and deleting the amino acids 91--124 disrupts binding of YopK to MATN2. A yopK null mutant exhibits hyper-adhesive phenotype, which could be responsible for the established Yop hyper-translocation phenotype of yopK mutant...
May 22, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533375/keap1-modifying-small-molecule-reveals-muted-nrf2-signaling-responses-in-neural-stem-cells-from-huntington-s-disease-patients
#3
Luisa Quinti, Sharadha Dayalan Naidu, Ulrike Träger, Xiqun Chen, Kimberly Kegel-Gleason, David Llères, Colúm Connolly, Vanita Chopra, Cho Low, Sébastien Moniot, Ellen Sapp, Adelaide R Tousley, Petr Vodicka, Michael J Van Kanegan, Linda S Kaltenbach, Lisa A Crawford, Matthew Fuszard, Maureen Higgins, James R C Miller, Ruth E Farmer, Vijay Potluri, Susanta Samajdar, Lisa Meisel, Ningzhe Zhang, Andrew Snyder, Ross Stein, Steven M Hersch, Lisa M Ellerby, Eranthie Weerapana, Michael A Schwarzschild, Clemens Steegborn, Blair R Leavitt, Alexei Degterev, Sarah J Tabrizi, Donald C Lo, Marian DiFiglia, Leslie M Thompson, Albena T Dinkova-Kostova, Aleksey G Kazantsev
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism by which this molecule activates NRF2 signaling. In a highly selective manner, the compound covalently modifies a critical stress-sensor cysteine (C151) of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#4
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#5
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/28529512/toll-interacting-protein-in-resolving-and-non-resolving-inflammation
#6
REVIEW
Elizabeth J A Kowalski, Liwu Li
Innate leukocytes manifest dynamic and distinct inflammatory responses upon challenges with rising dosages of pathogen-associated molecular pattern molecules such as lipopolysaccharide (LPS). To differentiate signal strengths, innate leukocytes may utilize distinct intracellular signaling circuitries modulated by adaptor molecules. Toll-interacting protein (Tollip) is one of the critical adaptor molecules potentially playing key roles in modulating the dynamic adaptation of innate leukocytes to varying dosages of external stimulants...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28529112/myeloid-differentiation-factor-88-is-up-regulated-in-epileptic-brain-and-contributes-to-experimental-seizures-in-rats
#7
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
#8
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
#9
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
#10
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/28527239/the-structure-of-a-lair1-containing-human-antibody-reveals-a-novel-mechanism-of-antigen-recognition
#11
Fu-Lien Hsieh, Matthew K Higgins
Antibodies are critical components of the human adaptive immune system, providing versatile scaffolds to display diverse antigen binding surfaces. Nevertheless, most antibodies have similar architectures, with the variable immunoglobulin domains of the heavy and light chain each providing three hypervariable loops, which are varied to generate diversity. The recent identification of a novel class of antibody in humans from malaria endemic regions of Africa was therefore surprising as one hypervariable loop contains the entire collagen-binding domain of human LAIR1...
May 20, 2017: ELife
https://www.readbyqxmd.com/read/28526927/sodium-thiosulphate-attenuates-brain-inflammation-induced-by-systemic-lipopolysaccharide-administration-in-c57bl-6j-mice
#12
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/28526415/lnk-deficiency-aggregates-palmitate-induced-preadipocyte-apoptosis
#13
Jie-Yi Du, Chen-Chen Jin, Guo-Hao Wang, Xiong-Qing Huang, Jian-Ding Cheng, Xue-Jun Wen, Xiao-Miao Zhao, Guan-Lei Wang
LNK (SH2B3) is an intracellular adaptor protein that negatively regulates cellular proliferation or self-renewal of hematopoietic stem cells and some other progenitor cells. LNK is also recognized as a key regulator of insulin resistance and inflammatory responses in several tissues and organs. It is unknown the function of LNK in adipose tissue. We previously demonstrated that type 2 diabetes mellitus (T2DM) mouse model had elevated serum free fatty acids (FFAs) levels and increased preadipocyte apoptosis in visceral fat tissue, showing the occurrence of lipotoxicity...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526413/tcr-crosslinking-promotes-crk-adaptor-protein-binding-to-tyrosine-phosphorylated-cd3%C3%AE-chain
#14
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/28526412/adaptor-proteins-gir1-and-gir2-ii-interaction-with-the-co-repressor-topless-and-promotion-of-histone-deacetylation-of-target-chromatin
#15
Renhong Wu, Vitaly Citovsky
Understanding how root hair development is controlled is important for understanding of many fundamental aspects of plant biology. Previously, we identified two plant-specific adaptor proteins GIR1 and GIR2 that interact with the major regulator of root hair development GL2 and suppress formation of root hair. Here, we show that GIR1 and GIR2 also interact with the co-repressor TOPLESS (TPL). This interaction required the GIR1 protein EAR motif, and was essential for the transcriptional repressor activity of GIR1...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526410/adaptor-proteins-gir1-and-gir2-i-interaction-with-the-repressor-glabra2-and-regulation-of-root-hair-development
#16
Renhong Wu, Vitaly Citovsky
Plants use specialized root outgrowths, termed root hairs, to enhance acquisition of nutrients and water, help secure anchorage, and facilitate interactions with soil microbiome. One of the major regulators of this process is GLABRA2 (GL2), a transcriptional repressor of root hair differentiation. However, regulation of the GL2-function is relatively well characterized, it remains completely unknown whether GL2 itself functions in complex with other transcriptional regulators. We identified GIR1 and GIR2, a plant-specific two-member family of closely related proteins that interact with GL2...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28523271/the-protein-chaperone-clpx-targets-native-and-non-native-aggregated-substrates-for-remodeling-disassembly-and-degradation-with-clpp
#17
Christopher J LaBreck, Shannon May, Marissa G Viola, Joseph Conti, Jodi L Camberg
ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28522851/mouse-rif1-is-a-regulatory-subunit-of-protein-phosphatase-1-pp1
#18
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/28522807/traf3-enhances-tcr-signaling-by-regulating-the-inhibitors-csk-and-ptpn22
#19
Alicia M Wallis, Ellie C Wallace, Bruce S Hostager, Zuoan Yi, Jon C D Houtman, Gail A Bishop
The adaptor protein TNF receptor associated factor (TRAF) 3 is required for effective TCR signaling and normal T cell effector functions, and associates with the CD3/CD28 complex upon activation. To determine how TRAF3 promotes proximal TCR signaling, we studied TRAF3-deficient mouse and human T cells, which showed a marked reduction in activating phosphorylation of the TCR-associated kinase Lck. The impact of TRAF3 on this very early signaling event led to the hypothesis that TRAF3 restrains one or both of two known inhibitors of Lck, C-terminal Src kinase (Csk) and protein tyrosine phosphatase N22 (PTPN22)...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521084/design-of-modular-protein-tags-for-the-orthogonal-covalent-bond-formation-at-specific-dna-sequences
#20
Thang Minh Nguyen, Eiji Nakata, Masayuki Saimura, Huyen Dinh, Takashi Morii
Simultaneous formation of specific covalent linkages at nucleotides in given DNA sequences demand distinct orthogonal reactivity of DNA modification agents. Such highly specific reactions require well-balanced reactivity and affinity of the DNA modification agents. Conjugation of a sequence-specific DNA binding zinc finger protein and a self-ligating protein-tag provides a modular adaptor that expedites formation of a covalent bond between the protein-tag and a substrate-modified nucleotide at a specific DNA sequence...
May 18, 2017: Journal of the American Chemical Society
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