Type I IFN Receptor-Signaling Complex Functions As a Scaffold
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Erb‑B2 Receptor Tyrosine Kinase 2 Is Negatively Regulated by the P53‑Responsive Microrna‑3184‑5P in Cervical Cancer Cells
ONCOLOGY REPORTS 45: 95-106, 2021 Erb‑B2 Receptor Tyrosine Kinase 2 is negatively regulated by the p53‑responsive microRNA‑3184‑5p in cervical cancer cells HONGLI LIU1, YUZHI LI1, JING ZHANG1, NAN WU2, FEI LIU2, LIHUA WANG1, YUAN ZHANG1, JING LIU1, XUAN ZHANG3, SUYANG GUO1 and HONGTAO WANG4 Departments of 1Gynecological Oncology and 2Respiration and Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, First Affiliated Hospital of Bengbu Medical College; Departments of3 Gynecological Oncology and 4Immunology and Anhui Key Laboratory of Infection and Immunity, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China Received November 30, 2019; Accepted October 2, 2020 DOI: 10.3892/or.2020.7862 Abstract. The oncogenic role of Erb-B2 Receptor Tyrosine Introduction Kinase 2 (ERBB2) has been identified in several types of cancer, but less is known on its function and mechanism of Among women, cervical cancer is ranked 4th in global action in cervical cancer cells. The present study employed cancer-associated deaths (1), with over half a million deaths a multipronged approach to investigate the role of ERBB2 in in 2012 (2). Cervical cancer can be broadly categorized into cervical cancer. ERBB2 and microRNA (miR)-3184-5p expres- squamous cell carcinoma, which constitutes the majority of sion was assessed in patient-derived cervical cancer biopsy cases (70-80%) or adenocarcinoma, which comprises 10-15% tissues, revealing that higher levels of ERBB2 and lower levels of cases (3). Cervical cancer is frequently caused by the of miR-3184-5p were associated with clinicopathological indi- oncovirus human papillomavirus (HPV), mainly by types cators of cervical cancer progression. -
The Wnt Pathway Scaffold Protein Axin Promotes Signaling Specificity by Suppressing Competing Kinase Reactions
bioRxiv preprint doi: https://doi.org/10.1101/768242; this version posted September 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The Wnt pathway scaffold protein Axin promotes signaling specificity by suppressing competing kinase reactions Maire Gavagan1,2, Erin Fagnan1,2, Elizabeth B. Speltz1, and Jesse G. Zalatan1,* 1Department of Chemistry, University of Washington, Seattle, WA 98195, USA 2These authors contributed equally to this work *Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/768242; this version posted September 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract GSK3β is a multifunctional kinase that phosphorylates β-catenin in the Wnt signaling network and also acts on other protein targets in response to distinct cellular signals. To test the long-standing hypothesis that the scaffold protein Axin specifically accelerates β-catenin phosphorylation, we measured GSK3β reaction rates with multiple substrates in a minimal, biochemically-reconstituted system. We observed an unexpectedly small, ~2-fold Axin-mediated rate increase for the β-catenin reaction. The much larger effects reported previously may have arisen because Axin can rescue GSK3β from an inactive state that occurs only under highly specific conditions. -
CK1 Is Required for a Mitotic Checkpoint That Delays Cytokinesis
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Current Biology 23, 1920–1926, October 7, 2013 ª2013 Elsevier Ltd All rights reserved http://dx.doi.org/10.1016/j.cub.2013.07.077 Report CK1 Is Required for a Mitotic Checkpoint that Delays Cytokinesis Alyssa E. Johnson,1 Jun-Song Chen,1 isoforms were detected, which collapsed into a discrete ladder and Kathleen L. Gould1,* upon phosphatase treatment (Figure 1A, lanes 1 and 2). These 1Department of Cell and Developmental Biology, Vanderbilt bands are ubiquitinated isoforms because they collapse into a University School of Medicine, Nashville, TN 37232, USA single band in the absence of dma1+ (Figure 1A, lane 4) and Dma1 is required for Sid4 ubiquitination [6]. In dma1D cells, a single slower-migrating form of Sid4 was detected, which Summary was collapsed by phosphatase treatment, indicating that Sid4 is phosphorylated in vivo (Figure 1A, lanes 3 and 4). In vivo Failure to accurately partition genetic material during cell radiolabeling experiments validated Sid4 as a phosphoprotein division causes aneuploidy and drives tumorigenesis [1]. and revealed that Sid4 is phosphorylated on serines and thre- Cell-cycle checkpoints safeguard cells from such catastro- onines (see Figures S1A–S1C available online). The constitu- phes by impeding cell-cycle progression when mistakes tive presence of an unmodified Sid4 isoform indicates that arise. FHA-RING E3 ligases, including human RNF8 [2] and only a subpopulation of Sid4 is modified (Figure 1A). Collec- CHFR [3] and fission yeast Dma1 [4], relay checkpoint signals tively, these data indicate that Sid4 is ubiquitinated and phos- by binding phosphorylated proteins via their FHA domains phorylated in vivo. -
JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors
Drugs https://doi.org/10.1007/s40265-020-01261-8 CURRENT OPINION JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors Miguel Nogueira1 · Luis Puig2 · Tiago Torres1,3 © Springer Nature Switzerland AG 2020 Abstract Despite advances in the treatment of psoriasis, there is an unmet need for efective and safe oral treatments. The Janus Kinase– Signal Transducer and Activator of Transcription (JAK–STAT) pathway plays a signifcant role in intracellular signalling of cytokines of numerous cellular processes, important in both normal and pathological states of immune-mediated infamma- tory diseases. Particularly in psoriasis, where the interleukin (IL)-23/IL-17 axis is currently considered the crucial pathogenic pathway, blocking the JAK–STAT pathway with small molecules would be expected to be clinically efective. However, relative non-specifcity and low therapeutic index of the available JAK inhibitors have delayed their integration into the therapeutic armamentarium of psoriasis. Current research appears to be focused on Tyrosine kinase 2 (TYK2), the frst described member of the JAK family. Data from the Phase II trial of BMS-986165—a selective TYK2 inhibitor—in psoriasis have been published and clinical results are encouraging, with a large Phase III programme ongoing. Further, the selective TYK2 inhibitor PF-06826647 is being tested in moderate-to-severe psoriasis in a Phase II clinical trial. Brepocitinib, a potent TYK2/JAK1 inhibitor, is also being evaluated, as both oral and topical treatment. Results of studies with TYK2 inhibitors will be important in assessing the clinical efcacy and safety of these drugs and their place in the therapeutic armamentarium of psoriasis. -
JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: a Focus on the Present and an Outlook on the Future
biomolecules Review JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future 1, 2, , 3 1,4 Jacopo Angelini y , Rossella Talotta * y , Rossana Roncato , Giulia Fornasier , Giorgia Barbiero 1, Lisa Dal Cin 1, Serena Brancati 1 and Francesco Scaglione 5 1 Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20133 Milan, Italy; [email protected] (J.A.); [email protected] (G.F.); [email protected] (G.B.); [email protected] (L.D.C.); [email protected] (S.B.) 2 Department of Clinical and Experimental Medicine, Rheumatology Unit, AOU “Gaetano Martino”, University of Messina, 98100 Messina, Italy 3 Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Pordenone, 33081 Aviano, Italy; [email protected] 4 Pharmacy Unit, IRCCS-Burlo Garofolo di Trieste, 34137 Trieste, Italy 5 Head of Clinical Pharmacology and Toxicology Unit, Grande Ospedale Metropolitano Niguarda, Department of Oncology and Onco-Hematology, Director of Postgraduate School of Clinical Pharmacology and Toxicology, University of Milan, 20162 Milan, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-090-2111; Fax: +39-090-293-5162 Co-first authors. y Received: 16 May 2020; Accepted: 1 July 2020; Published: 5 July 2020 Abstract: Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. -
Supplementary Materials
Supplementary Suppl. Figure 1: MAPK signalling pathway of A: NCI-H2502, B: NCI-H2452, C: MSTO-211H and D: MRC-5. Suppl. Figure 2: Cell cycle pathway of A: NCI-H2502, B: NCI-H2452, C: MSTO-211H and D: MRC- 5. Suppl. Figure 3: Cancer pathways of A: NCI-H2502, B: NCI-H2452, C: MSTO-211H and D: MRC-5. Suppl. Figure 4: Phosphorylation level of A: ARAF, B: EPHA1, C: EPHA2, D: EPHA7 in all cell lines. For each cell line, phosphorylation levels are depicted before (Medium) and after cisplatin treatment (Cis). Suppl. Figure 5: Phosphorylation Level of A: KIT, B: PTPN11, C: PIK3R1, D: PTPN6 in all cell lines. For each cell line, phosphorylation levels are depicted before (Medium) and after cisplatin treatment (Cis). Suppl. Figure 6: Phosphorylation Level of A: KDR, B: EFS, C: AKT1, D: PTK2B/FAK2 in all cell lines. For each cell line, phosphorylation levels are depicted before (Medium) and after cisplatin treatment (Cis). Suppl. Figure 7: Scoreplots and volcanoplots of PTK upstream kinase analysis: A: Scoreplot of PTK- Upstream kinase analysis for NCI-H2052 cells. B: Volcanoplot of PTK-Upstream kinase analysis for NCI-H2052 cells. C: Scoreplot of PTK-Upstream kinase analysis for NCI-H2452 cells. D: Volcanoplot of PTK-Upstream kinase analysis for NCI-H2452 cells. E: Scoreplot of PTK-Upstream kinase analysis for MSTO-211H cells. F: Volcanoplot of PTK-Upstream kinase analysis for MSTO- 211H cells. G: Scoreplot of PTK-Upstream kinase analysis for MRC-5cells. H: Volcanoplot of PTK- Upstream kinase analysis for MRC-5 cells. Suppl. Figure 8: Scoreplots and volcanoplots of STK upstream kinase analysis: A: Scoreplot of STK- Upstream kinase analysis for NCI-H2052 cells. -
Biomarker Testing in Non- Small Cell Lung Cancer (NSCLC)
The biopharma business of Merck KGaA, Darmstadt, Germany operates as EMD Serono in the U.S. and Canada. Biomarker testing in non- small cell lung cancer (NSCLC) Copyright © 2020 EMD Serono, Inc. All rights reserved. US/TEP/1119/0018(1) Lung cancer in the US: Incidence, mortality, and survival Lung cancer is the second most common cancer diagnosed annually and the leading cause of mortality in the US.2 228,820 20.5% 57% Estimated newly 5-year Advanced or 1 survival rate1 metastatic at diagnosed cases in 2020 diagnosis1 5.8% 5-year relative 80-85% 2 135,720 survival with NSCLC distant disease1 Estimated deaths in 20201 2 NSCLC, non-small cell lung cancer; US, United States. 1. National Institutes of Health (NIH), National Cancer Institute. Cancer Stat Facts: Lung and Bronchus Cancer website. www.seer.cancer.gov/statfacts/html/lungb.html. Accessed May 20, 2020. 2. American Cancer Society. What is Lung Cancer? website. https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed May 20, 2020. NSCLC is both histologically and genetically diverse 1-3 NSCLC distribution by histology Prevalence of genetic alterations in NSCLC4 PTEN 10% DDR2 3% OTHER 25% PIK3CA 12% LARGE CELL CARCINOMA 10% FGFR1 20% SQUAMOUS CELL CARCINOMA 25% Oncogenic drivers in adenocarcinoma Other or ADENOCARCINOMA HER2 1.9% 40% KRAS 25.5% wild type RET 0.7% 55% NTRK1 1.7% ROS1 1.7% Oncogenic drivers in 0% 20% 40% 60% RIT1 2.2% squamous cell carcinoma Adenocarcinoma DDR2 2.9% Squamous cell carcinoma NRG1 3.2% Large cell carcinoma -
HCC and Cancer Mutated Genes Summarized in the Literature Gene Symbol Gene Name References*
HCC and cancer mutated genes summarized in the literature Gene symbol Gene name References* A2M Alpha-2-macroglobulin (4) ABL1 c-abl oncogene 1, receptor tyrosine kinase (4,5,22) ACBD7 Acyl-Coenzyme A binding domain containing 7 (23) ACTL6A Actin-like 6A (4,5) ACTL6B Actin-like 6B (4) ACVR1B Activin A receptor, type IB (21,22) ACVR2A Activin A receptor, type IIA (4,21) ADAM10 ADAM metallopeptidase domain 10 (5) ADAMTS9 ADAM metallopeptidase with thrombospondin type 1 motif, 9 (4) ADCY2 Adenylate cyclase 2 (brain) (26) AJUBA Ajuba LIM protein (21) AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 (4) Akt AKT serine/threonine kinase (28) AKT1 v-akt murine thymoma viral oncogene homolog 1 (5,21,22) AKT2 v-akt murine thymoma viral oncogene homolog 2 (4) ALB Albumin (4) ALK Anaplastic lymphoma receptor tyrosine kinase (22) AMPH Amphiphysin (24) ANK3 Ankyrin 3, node of Ranvier (ankyrin G) (4) ANKRD12 Ankyrin repeat domain 12 (4) ANO1 Anoctamin 1, calcium activated chloride channel (4) APC Adenomatous polyposis coli (4,5,21,22,25,28) APOB Apolipoprotein B [including Ag(x) antigen] (4) AR Androgen receptor (5,21-23) ARAP1 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 (4) ARHGAP35 Rho GTPase activating protein 35 (21) ARID1A AT rich interactive domain 1A (SWI-like) (4,5,21,22,24,25,27,28) ARID1B AT rich interactive domain 1B (SWI1-like) (4,5,22) ARID2 AT rich interactive domain 2 (ARID, RFX-like) (4,5,22,24,25,27,28) ARID4A AT rich interactive domain 4A (RBP1-like) (28) ARID5B AT rich interactive domain 5B (MRF1-like) (21) ASPM Asp (abnormal -
Impact of Digestive Inflammatory Environment and Genipin
International Journal of Molecular Sciences Article Impact of Digestive Inflammatory Environment and Genipin Crosslinking on Immunomodulatory Capacity of Injectable Musculoskeletal Tissue Scaffold Colin Shortridge 1, Ehsan Akbari Fakhrabadi 2 , Leah M. Wuescher 3 , Randall G. Worth 3, Matthew W. Liberatore 2 and Eda Yildirim-Ayan 1,4,* 1 Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH 43606, USA; [email protected] 2 Department of Chemical Engineering, College of Engineering, University of Toledo, Toledo, OH 43606, USA; [email protected] (E.A.F.); [email protected] (M.W.L.) 3 Department of Medical Microbiology and Immunology, University of Toledo, Toledo, OH 43614, USA; [email protected] (L.M.W.); [email protected] (R.G.W.) 4 Department of Orthopaedic Surgery, University of Toledo Medical Center, Toledo, OH 43614, USA * Correspondence: [email protected]; Tel.: +1-419-530-8257; Fax: +1-419-530-8030 Abstract: The paracrine and autocrine processes of the host response play an integral role in the success of scaffold-based tissue regeneration. Recently, the immunomodulatory scaffolds have received huge attention for modulating inflammation around the host tissue through releasing anti- inflammatory cytokine. However, controlling the inflammation and providing a sustained release of anti-inflammatory cytokine from the scaffold in the digestive inflammatory environment are predicated upon a comprehensive understanding of three fundamental questions. (1) How does the Citation: Shortridge, C.; Akbari release rate of cytokine from the scaffold change in the digestive inflammatory environment? (2) Fakhrabadi, E.; Wuescher, L.M.; Can we prevent the premature scaffold degradation and burst release of the loaded cytokine in the Worth, R.G.; Liberatore, M.W.; digestive inflammatory environment? (3) How does the scaffold degradation prevention technique Yildirim-Ayan, E. -
Supplementary Table 1. in Vitro Side Effect Profiling Study for LDN/OSU-0212320. Neurotransmitter Related Steroids
Supplementary Table 1. In vitro side effect profiling study for LDN/OSU-0212320. Percent Inhibition Receptor 10 µM Neurotransmitter Related Adenosine, Non-selective 7.29% Adrenergic, Alpha 1, Non-selective 24.98% Adrenergic, Alpha 2, Non-selective 27.18% Adrenergic, Beta, Non-selective -20.94% Dopamine Transporter 8.69% Dopamine, D1 (h) 8.48% Dopamine, D2s (h) 4.06% GABA A, Agonist Site -16.15% GABA A, BDZ, alpha 1 site 12.73% GABA-B 13.60% Glutamate, AMPA Site (Ionotropic) 12.06% Glutamate, Kainate Site (Ionotropic) -1.03% Glutamate, NMDA Agonist Site (Ionotropic) 0.12% Glutamate, NMDA, Glycine (Stry-insens Site) 9.84% (Ionotropic) Glycine, Strychnine-sensitive 0.99% Histamine, H1 -5.54% Histamine, H2 16.54% Histamine, H3 4.80% Melatonin, Non-selective -5.54% Muscarinic, M1 (hr) -1.88% Muscarinic, M2 (h) 0.82% Muscarinic, Non-selective, Central 29.04% Muscarinic, Non-selective, Peripheral 0.29% Nicotinic, Neuronal (-BnTx insensitive) 7.85% Norepinephrine Transporter 2.87% Opioid, Non-selective -0.09% Opioid, Orphanin, ORL1 (h) 11.55% Serotonin Transporter -3.02% Serotonin, Non-selective 26.33% Sigma, Non-Selective 10.19% Steroids Estrogen 11.16% 1 Percent Inhibition Receptor 10 µM Testosterone (cytosolic) (h) 12.50% Ion Channels Calcium Channel, Type L (Dihydropyridine Site) 43.18% Calcium Channel, Type N 4.15% Potassium Channel, ATP-Sensitive -4.05% Potassium Channel, Ca2+ Act., VI 17.80% Potassium Channel, I(Kr) (hERG) (h) -6.44% Sodium, Site 2 -0.39% Second Messengers Nitric Oxide, NOS (Neuronal-Binding) -17.09% Prostaglandins Leukotriene, -
Crosstalk Between Casein Kinase II and Ste20-Related Kinase Nak1
University of Massachusetts Medical School eScholarship@UMMS GSBS Student Publications Graduate School of Biomedical Sciences 2013-03-05 Crosstalk between casein kinase II and Ste20-related kinase Nak1 Lubos Cipak University of Vienna Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_sp Part of the Biochemistry Commons, Cell Biology Commons, Cellular and Molecular Physiology Commons, and the Molecular Biology Commons Repository Citation Cipak L, Gupta S, Rajovic I, Jin Q, Anrather D, Ammerer G, McCollum D, Gregan J. (2013). Crosstalk between casein kinase II and Ste20-related kinase Nak1. GSBS Student Publications. https://doi.org/ 10.4161/cc.24095. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1850 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Student Publications by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. EXTRA VIEW Cell Cycle 12:6, 884–888; March 15, 2013; © 2013 Landes Bioscience Crosstalk between casein kinase II and Ste20-related kinase Nak1 Lubos Cipak,1,2,† Sneha Gupta,3,† Iva Rajovic,1 Quan-Wen Jin,3,4 Dorothea Anrather,1 Gustav Ammerer,1 Dannel McCollum3,* and Juraj Gregan1,5,* 1Max F. Perutz Laboratories; Department of Chromosome Biology; University of Vienna; Vienna, Austria; 2Cancer Research Institute; Slovak Academy of Sciences; Bratislava, Slovak Republic; 3Department of Microbiology and Physiological Systems and Program in Cell Dynamics; University of Massachusetts Medical School; Worcester, MA USA; 4Department of Biological Medicine; School of Life Sciences; Xiamen University; Xiamen, China; 5Department of Genetics; Comenius University; Bratislava, Slovak Republic †These authors contributed equally to this work. -
Electrical Synaptic Transmission Requires a Postsynaptic Scaffolding Protein
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.03.410696; this version posted December 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. TITLE: Electrical synaptic transmission requires a postsynaptic scaffolding protein Abagael M. Lasseigne1*, Fabio A. Echeverry2*, Sundas Ijaz2*, Jennifer Carlisle Michel1*, E. Anne Martin1, Audrey J. Marsh1, Elisa Trujillo1, Kurt C. Marsden3, Alberto E. Pereda2#, Adam C. Miller1#@ * denotes co-first author # denotes co-corresponding author @ denotes lead contact Affiliations: 1 Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA 2 Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA 3 Department of Biological Sciences, NC State University, Raleigh, NC 27695, USA Correspondence: [email protected] [email protected] Keywords: gap junction; connexin; ZO1 ZO-1; synaptic development; electrical coupling 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.12.03.410696; this version posted December 4, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. SUMMARY Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support.