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In vivo protein protein interaction

Elizabeth A Simonik, Ying Cai, Katherine N Kimmelshue, Dana M Brantley-Sieders, Holli A Loomans, Claudia D Andl, Grant M Westlake, Victoria M Youngblood, Jin Chen, Wendell G Yarbrough, Brandee T Brown, Lalitha Nagarajan, Stephen J Brandt
Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease...
2016: PloS One
Juan M González-Morena, María I Montañez, Giancarlo Aldini, Francisco J Sánchez-Gómez, Dolores Pérez-Sala
Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be life-threatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions...
September 27, 2016: Current Pharmaceutical Design
Patrick Antonietti, Benedikt Linder, Stephanie Hehlgans, Iris C Mildenberger, Michael C Burger, Simone Fulda, Joachim P Steinbach, Florian Gessler, Franz Rodel, Michel Mittelbronn, Donat Kogel
Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 (heat shock factor 1) acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101-induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, while these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels...
October 24, 2016: Molecular Cancer Therapeutics
Castrese Morrone, Riccardo Miggiano, Mario Serpe, Alberto Massarotti, Anna Valenti, Giovanni Del Monaco, Mosè Rossi, Franca Rossi, Menico Rizzi, Giuseppe Perugino, Maria Ciaramella
BACKGROUND: Alkylated DNA-protein alkyltransferases (AGTs) are conserved proteins that repair alkylation damage in DNA by using a single-step mechanism leading to irreversible alkylation of the catalytic cysteine in the active site. Trans-alkylation induces inactivation and destabilization of the protein, both in vitro and in vivo, likely triggering conformational changes. A complete picture of structural rearrangements occurring during the reaction cycle is missing, despite considerable interest raised by the peculiarity of AGT reaction, and the contribution of a functional AGT in limiting the efficacy of chemotherapy with alkylating drugs...
October 21, 2016: Biochimica et Biophysica Acta
Alexander Rebl, Henrike Rebl, Judith M Köbis, Tom Goldammer, Hans-Martin Seyfert
The mammalian interleukin 1 receptor-like 1 receptor (IL1RL1), commonly known as ST2, is thought to downregulate TLR signalling by sequestering the signalling adapter MYD88 (myeloid differentiation primary response protein 88). ST2 sequences are known in several fish species, but none of them have functionally been examined. We characterised ST2 from rainbow trout (Oncorhynchus mykiss) and the structure of its encoding gene. The primary sequence of ST2 is only weakly conserved from fish to human. However, the amino acid sequences forming the interfaces for ST2 and MYD88 interaction are well conserved throughout evolution...
October 21, 2016: Developmental and Comparative Immunology
Jinfeng Kong, Juan Du, Yunling Wang, Mingzi Yang, Jianchao Gao, Xiaofan Wei, Weigang Fang, Jun Zhan, Hongquan Zhang
Kindlin-1, an integrin-interacting protein, has been implicated in TGF-β/Smad3 signaling. However, the molecular mechanism underlying Kindlin-1 regulation of TGF-β/Smad3 signaling remains elusive. Here, we reported that Kindlin-1 is an important mediator of TGF-β/Smad3 signaling by showing that Kindlin-1 physically interacts with TGF-β receptor I (TβRI), Smad anchor for receptor activation (SARA) and Smad3. Kindlin-1 is required for the interaction of Smad3 with TβRI, Smad3 phosphorylation, nuclear translocation, and finally the activation of TGF-β/Smad3 signaling pathway...
October 20, 2016: Oncotarget
Alexandre Chlenski, Marija Dobratic, Helen R Salwen, Mark Applebaum, Lisa J Guerrero, Ryan Miller, Gillian DeWane, Elena Solomaha, Jeremy D Marks, Susan L Cohn
SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation...
October 20, 2016: Oncotarget
Andreas Gollner, Dorothea Rudolph, Heribert Arnhof, Markus Bauer, Sophia Maria Blake, Guido Boehmelt, Xiao-Ling Cockcroft, Georg Dahmann, Peter Ettmayer, Thomas Gerstberger, Jale Karolyi-Oezguer, Dirk Kessler, Christiane Kofink, Juergen Ramharter, Jörg Rinnenthal, Alexander Savchenko, Renate Schnitzer, Harald Weinstabl, Ulrike Weyer-Czernilofsky, Tobias Wunberg, Darryl B McConnell
Scaffold modification based on Wang´s pioneering MDM2-p53 inhibitors led to novel, chemically stable spiro-oxindole compounds bearing a spiro[3H-indole-3,2´-pyrrolidin]-2(1H)-one scaffold that are not prone to epimerization as observed for the initial spiro[3H-indole-3,3´-pyrrolidin]-2(1H)-one scaffold. Further structure based optimization inspired by natural product architectures led to a complex fused ring system ideally suited to bind to the MDM2 protein and to interrupt its protein-protein interaction (PPI) with TP53...
October 24, 2016: Journal of Medicinal Chemistry
Kathryn M Kingsmore, Daniel K Logsdon, Desiree H Floyd, Shayn M Peirce, Benjamin W Purow, Jennifer M Munson
Glioblastoma (GBM) prognosis remains dismal due in part to the invasiveness of GBM cells. Interstitial fluid flow (IFF) has been shown to increase invasion of glioma cells in vitro through the CXCR4 receptor interacting with autologous, pericellular gradients of CXCL12 (autologous chemotaxis) or through the CD44 receptor interactions with the extracellular matrix (hyaluronan-mediated mechanotransduction). These mechanisms have not been examined together and thus we hypothesized that both mechanisms contribute to invasion in populations of cancer cells...
October 24, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Maarten A A van de Klundert, Maartje van den Biggelaar, Neeltje A Kootstra, Hans L Zaaijer
In the infected human hepatocyte, expression of the hepatitis B virus (HBV) accessory protein X (HBx) is essential to maintain viral replication in vivo. HBx critically interacts with the host damaged DNA binding protein 1 (DDB1) and the associated ubiquitin ligase machinery, suggesting that HBx functions by inducing the degradation of host proteins. To identify such host proteins, we systematically analyzed the HBx interactome. One HBx interacting protein, talin-1 (TLN1), was proteasomally degraded upon HBx expression...
October 19, 2016: Viruses
Jin-Zhao Ma, Fu Yang, Chuan-Chuan Zhou, Feng Liu, Ji-Hang Yuan, Fang Wang, Tian-Tian Wang, Qing-Guo Xu, Wei-Ping Zhou, Shu-Han Sun
: M(6) A modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m(6) A modifications are decreased in HCC, especially in metastatic HCC, and that METTL14 is the main factor involved in aberrant m(6) A modification. Moreover, METTL14 down-regulation acts as an adverse prognosis factor for recurrence-free survival (RFS) of HCC and is significantly associated with tumour metastasis in vitro and in vivo...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
ChunSik Choe, Jürgen Lademann, Maxim E Darvin
Confocal Raman microscopy has been used to measure depth-dependent profiles of human SC in vivo in the high wavenumber (HWN) region. In order to keep the linearity of HWN region boundaries and to not remove an informative signal from Raman spectra, a new baseline subtraction procedure has been introduced. After baseline subtraction, the HWN spectrum was deconvoluted using 10 Gaussian functions with individual chemical meanings. The results show that the hydrogen bound water molecule types contributed differently to the water diffusion process in the SC...
October 24, 2016: Analyst
Makoto Hirano, Kiichiro Totani, Tomohiko Fukuda, Jianguo Gu, Akemi Suzuki
BACKGROUND: Megalin is a 600-kDa single-spanning transmembrane glycoprotein and functions as an endocytic receptor, distributed not only in the kidney but also in other tissues. Structurally and functionally distinct ligands for megalin have been identified. Megalin has 30 potential N-glycosylation sites in its extracellular domain. We found that megalin interacts with its ligands in a glycoform-dependent manner. METHODS: Distribution of megalin and glycans was histochemically analyzed in mouse kidneys...
October 20, 2016: Biochimica et Biophysica Acta
Phakhamon Lapphanichayakool, Manote Sutheerawattananonda, Nanteetip Limpeanchob
The beneficial effect of cholesterol-lowering proteins and/or peptides derived from various dietary sources is continuously reported. A non-dietary protein from silk cocoon, sericin, has also demonstrated cholesterol-lowering activity. A sericin hydrolysate prepared by enzymatic hydrolysis was also expected to posses this effect. The present study was aimed at investigating the cholesterol-lowering effect of sericin peptides, so called "sericin-derived oligopeptides" (SDO) both in vivo and in vitro. The results showed that SDO at all three doses tested (10 mg kg(-1) day(-1), 50 mg kg(-1) day(-1), and 200 mg kg(-1) day(-1)) suppressed serum total and non-HDL cholesterol levels in rats fed a high-cholesterol diet...
October 22, 2016: Journal of Natural Medicines
Jian Tang, Yingbin Ge, Lei Yang, Xinyu Xu, Tao Sui, Dawei Ge, Jun Que, Xiaojian Cao
BACKGROUND/AIMS: Hypertrophic scars (HS) formation results from reduced apoptosis and increased proliferation of fibroblasts. Therefore, apoptosis of fibroblasts is a key target for the development of novel therapeutic strategies for HS. Previous reports demonstrated that FK506 could attenuate scar formation in vivo and FK506 could also induce endoplasmic reticulum stress (ER stress). However, the effects of FK506 on ER stress-mediated apoptosis in fibroblasts remain unclear. METHODS: Rat skin fibroblasts were used in the study...
October 24, 2016: Cellular Physiology and Biochemistry
Adina R Bujold, Josée Labrie, Mario Jacques, Janet I MacInnes
Actinobacillus suis is an opportunistic pathogen that resides in the tonsils of the soft palate of swine. Unknown stimuli can cause this organism to invade the host, resulting in septicaemia and sequelae including death. To better understand its pathogenesis, the expression of several adhesin genes was evaluated by semi-quantitative real-time PCR in A. suis grown in conditions that mimic the host environment, including different nutrient and oxygen levels, exponential and stationary phases of growth, and in the presence of the stress hormone epinephrine...
November 15, 2016: Veterinary Microbiology
S Zappavigna, M Scuotto, A M Cossu, D Ingrosso, M De Rosa, C Schiraldi, R Filosa, M Caraglia
BACKGROUND: Embelin is a potent dual inhibitor of 5-lipoxigenase (5-LOX) and microsomal prostaglandin E2 synthase (mPGES)-1 that suppresses proliferation of human glioma cells and induces apoptosis by inhibiting XIAP and NF-κB signaling pathway. Synthetic structural modification yielded the derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id), an embelin constrained analogue, with improved efficiency against 5-LOX in human neutrophils and anti-inflammatory activity in vivo...
October 22, 2016: Journal of Experimental & Clinical Cancer Research: CR
Henryka Długońska, Justyna Gatkowska
Extracellular vesicles – EV’s, including exosomes, are known to be essential tools of intercellular communication, enabling the exchange of information without direct contact between cells. Exosomes are secreted both in vitro and in vivo by single- and multi-cellular organisms, regardless of their type, and play an essential role in cell-to-cell communication. EV’s may carry various materials and ongoing studies have provided a new insight into their potential participation in various critical biological processes, including carcinogenesis, protein trafficking, immunostimulation and pathogenesis of infectious diseases...
October 1, 2016: Annals of Parasitology
Yan Xu, Yawei Xing, Yanjie Xu, Chahua Huang, Huihui Bao, Kui Hong, Xiaoshu Cheng
We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis...
October 17, 2016: Environmental Toxicology and Pharmacology
Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang
: Bile acids (BAs) play critical physiological functions in cholesterol homeostasis and deregulation of BA metabolism causes cholestatic liver injury. Maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor, however its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG3RNA followed by mass spectrometry, we identified RNA binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interaction protein and validated their interaction by RNA immunoprecipitation (RIP)...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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