Collagens, Modifying Enzymes and Their Mutations in Humans, Flies And
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
New Concepts in Basement Membrane Biology Willi Halfter1, Philipp Oertle2, Christophe A
REVIEW ARTICLE New concepts in basement membrane biology Willi Halfter1, Philipp Oertle2, Christophe A. Monnier2,*, Leon Camenzind2, Magaly Reyes-Lua1, Huaiyu Hu3, Joseph Candiello4, Anatalia Labilloy5,†, Manimalha Balasubramani6, Paul Bernhard Henrich1 and Marija Plodinec2,7 1 Department of Ophthalmology, University Hospital Basel, Switzerland 2 Biozentrum and the Swiss Nanoscience Institute, University of Basel, Switzerland 3 Department of Neurobiology and Physiology, Upstate University Hospital, SUNY University, Syracuse, NY, USA 4 Department of Bioengeneering, University of Pittsburgh, PA, USA 5 Department of Renal Physiology, University of Pittsburgh, PA, USA 6 Proteomics Core Facility of the University of Pittsburgh, PA, USA 7 Department of Pathology, University Hospital Basel, Switzerland Keywords Basement membranes (BMs) are thin sheets of extracellular matrix that basal lamina; basement membrane; outline epithelia, muscle fibers, blood vessels and peripheral nerves. The biomechanical properties; collagen IV; current view of BM structure and functions is based mainly on transmis- laminin; membrane asymmetry; nidogen; sion electron microscopy imaging, in vitro protein binding assays, and phe- perlecan notype analysis of human patients, mutant mice and invertebrata. Correspondence Recently, MS-based protein analysis, biomechanical testing and cell adhe- W. Halfter, Department of Ophthalmology, sion assays with in vivo derived BMs have led to new and unexpected University Hospital Basel, Mittlere insights. Proteomic analysis combined with ultrastructural studies showed Strasse 91, 4031 Basel, Switzerland that many BMs undergo compositional and structural changes with Fax: +41 61 267 21 09 advancing age. Atomic force microscopy measurements in combination Tel: +49 7624 982528 with phenotype analysis have revealed an altered mechanical stiffness that E-mail: [email protected] M. -
Endostatin: a Novel Inhibitor of Androgen Receptor Function in Prostate Cancer
Endostatin: A novel inhibitor of androgen receptor function in prostate cancer Joo Hyoung Leea, Tatyana Isayevaa, Matthew R. Larsonb, Anandi Sawanta, Ha-Ram Chaa, Diptiman Chandaa, Igor N. Chesnokovc, and Selvarangan Ponnazhagana,1 Departments of aPathology and cBiochemistry and Molecular Genetics, University of Alabama, Birmingham, AL 35294; and bDepartment of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109 Edited* by Louise T. Chow, University of Alabama at Birmingham, Birmingham, AL, and approved December 29, 2014 (received for review September 12, 2014) Acquired resistance to androgen receptor (AR)-targeted therapies a C-terminal LBD. Like other nuclear receptors (NRs), AR is a compels the development of novel treatment strategies for castra- transcription factor regulating target-gene expression in a ligand- tion-resistant prostate cancer (CRPC). Here, we report a profound dependent manner (2, 16). Cognate ligand binding induces effect of endostatin on prostate cancer cells by efficient intracellular conformational changes predominantly in helix 12 of AR trafficking, direct interaction with AR, reduction of nuclear AR level, LBD, which enhances transcriptional activity by forming a ligand- and down-regulation of AR-target gene transcription. Structural dependent AF-2 binding interface for coactivators (17). Wilson modeling followed by functional analyses further revealed that and colleagues demonstrated that the interdomain interaction phenylalanine-rich α1-helix in endostatin—which shares struc- between AF-1 in NTD and AF-2 in LBD (N/C interaction) leads tural similarity with noncanonical nuclear receptor box in AR— to AR stabilization and slower ligand dissociation (18, 19). antagonizes AR transcriptional activity by occupying the activation Functional activity of AR largely depends on AF-2 that function (AF)-2 binding interface for coactivators and N-terminal accommodates the binding of various AR coactivators by rec- AR AF-1. -
Ophthalmological Features Associated with COL4A1 Mutations
OPHTHALMIC MOLECULAR GENETICS SECTION EDITOR: JANEY L. WIGGS, MD, PhD Ophthalmological Features Associated With COL4A1 Mutations Isabelle Coupry, PhD; Igor Sibon, MD, PhD; Bruno Mortemousque, MD; Franc¸ois Rouanet, MD; Manuele Mine, PharmD, PhD; Cyril Goizet, MD, PhD Objective: To investigate the wide variability of ocular Conclusions: The COL4A1 mutations may be associ- manifestations associated with mutations in the COL4A1 ated with various ophthalmologic developmental anoma- gene that encodes collagen IV␣1. lies of anterior segment dysgenesis type, which are reminiscent of Axenfeld-Rieger anomalies (ARA). Cere- Methods: We clinically evaluated 7 patients from 2 un- brovascular disorders should be added to the list of signs related families in whom ocular features segregated with potentially associated with ARA. COL4A1 mutations that were identified by direct se- quencing. Clinical Relevance: These data suggest that cerebral magnetic resonance imaging may be recommended in Results: The G2159A transition (c.2159GϾA) that leads the clinical treatment of patients with apparently iso- tothemissensemutationp.Gly720Aspwasidentifiedinfam- lated ARA, even when neurological symptoms or signs ily A. An ocular phenotype of variable severity was observed are lacking. in all affected relatives. The missense mutation c.2263GϾA, p.Gly755Arg was identified in family B. One patient from family B also displayed notable ocular features. Arch Ophthalmol. 2010;128(4):483-489 NEW FORM OF HEREDITARY constellation of ocular findings that in- cerebrovascular disorder clude anomalies of the anterior chamber was recently associated angle and aqueous drainage structures (iri- with mutations in the dogoniodysgenesis), iris hypoplasia, ec- COL4A1 gene that en- centric pupil (corectopia), iris tears (poly- Acodes collagen IV␣1.1,2 Mutations in coria), and iridocorneal adhesions COL4A1 were initially associated with ce- traversing the anterior chamber. -
A Collagen Glucosyltransferase Drives Lung Adenocarcinoma Progression in Mice
ARTICLE https://doi.org/10.1038/s42003-021-01982-w OPEN A collagen glucosyltransferase drives lung adenocarcinoma progression in mice Hou-Fu Guo 1, Neus Bota-Rabassedas 1, Masahiko Terajima 2, B. Leticia Rodriguez1, Don L. Gibbons 1, Yulong Chen1, Priyam Banerjee1, Chi-Lin Tsai 3, Xiaochao Tan1, Xin Liu1, Jiang Yu1, Michal Tokmina-Roszyk4, Roma Stawikowska4, Gregg B. Fields4, Mitchell D. Miller 5, Xiaoyan Wang3, Juhoon Lee6,7, Kevin N. Dalby6,7, Chad J. Creighton 8,9, George N. Phillips Jr 5,10, John A. Tainer 3, Mitsuo Yamauchi2 & ✉ Jonathan M. Kurie 1 Cancer cells are a major source of enzymes that modify collagen to create a stiff, fibrotic tumor stroma. High collagen lysyl hydroxylase 2 (LH2) expression promotes metastasis and 1234567890():,; is correlated with shorter survival in lung adenocarcinoma (LUAD) and other tumor types. LH2 hydroxylates lysine (Lys) residues on fibrillar collagen’s amino- and carboxy-terminal telopeptides to create stable collagen cross-links. Here, we show that electrostatic interac- tions between the LH domain active site and collagen determine the unique telopeptidyl lysyl hydroxylase (tLH) activity of LH2. However, CRISPR/Cas-9-mediated inactivation of tLH activity does not fully recapitulate the inhibitory effect of LH2 knock out on LUAD growth and metastasis in mice, suggesting that LH2 drives LUAD progression, in part, through a tLH- independent mechanism. Protein homology modeling and biochemical studies identify an LH2 isoform (LH2b) that has previously undetected collagen galactosylhydroxylysyl glucosyl- transferase (GGT) activity determined by a loop that enhances UDP-glucose-binding in the GLT active site and is encoded by alternatively spliced exon 13 A. -
Methylome and Transcriptome Maps of Human Visceral and Subcutaneous
www.nature.com/scientificreports OPEN Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal Received: 9 April 2019 Accepted: 11 June 2019 key epigenetic diferences at Published: xx xx xxxx developmental genes Stephen T. Bradford1,2,3, Shalima S. Nair1,3, Aaron L. Statham1, Susan J. van Dijk2, Timothy J. Peters 1,3,4, Firoz Anwar 2, Hugh J. French 1, Julius Z. H. von Martels1, Brodie Sutclife2, Madhavi P. Maddugoda1, Michelle Peranec1, Hilal Varinli1,2,5, Rosanna Arnoldy1, Michael Buckley1,4, Jason P. Ross2, Elena Zotenko1,3, Jenny Z. Song1, Clare Stirzaker1,3, Denis C. Bauer2, Wenjia Qu1, Michael M. Swarbrick6, Helen L. Lutgers1,7, Reginald V. Lord8, Katherine Samaras9,10, Peter L. Molloy 2 & Susan J. Clark 1,3 Adipocytes support key metabolic and endocrine functions of adipose tissue. Lipid is stored in two major classes of depots, namely visceral adipose (VA) and subcutaneous adipose (SA) depots. Increased visceral adiposity is associated with adverse health outcomes, whereas the impact of SA tissue is relatively metabolically benign. The precise molecular features associated with the functional diferences between the adipose depots are still not well understood. Here, we characterised transcriptomes and methylomes of isolated adipocytes from matched SA and VA tissues of individuals with normal BMI to identify epigenetic diferences and their contribution to cell type and depot-specifc function. We found that DNA methylomes were notably distinct between diferent adipocyte depots and were associated with diferential gene expression within pathways fundamental to adipocyte function. Most striking diferential methylation was found at transcription factor and developmental genes. Our fndings highlight the importance of developmental origins in the function of diferent fat depots. -
140503 IPF Signatures Supplement Withfigs Thorax
Supplementary material for Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis Daryle J. DePianto1*, Sanjay Chandriani1⌘*, Alexander R. Abbas1, Guiquan Jia1, Elsa N. N’Diaye1, Patrick Caplazi1, Steven E. Kauder1, Sabyasachi Biswas1, Satyajit K. Karnik1#, Connie Ha1, Zora Modrusan1, Michael A. Matthay2, Jasleen Kukreja3, Harold R. Collard2, Jackson G. Egen1, Paul J. Wolters2§, and Joseph R. Arron1§ 1Genentech Research and Early Development, South San Francisco, CA 2Department of Medicine, University of California, San Francisco, CA 3Department of Surgery, University of California, San Francisco, CA ⌘Current address: Novartis Institutes for Biomedical Research, Emeryville, CA. #Current address: Gilead Sciences, Foster City, CA. *DJD and SC contributed equally to this manuscript §PJW and JRA co-directed this project Address correspondence to Paul J. Wolters, MD University of California, San Francisco Department of Medicine Box 0111 San Francisco, CA 94143-0111 [email protected] or Joseph R. Arron, MD, PhD Genentech, Inc. MS 231C 1 DNA Way South San Francisco, CA 94080 [email protected] 1 METHODS Human lung tissue samples Tissues were obtained at UCSF from clinical samples from IPF patients at the time of biopsy or lung transplantation. All patients were seen at UCSF and the diagnosis of IPF was established through multidisciplinary review of clinical, radiological, and pathological data according to criteria established by the consensus classification of the American Thoracic Society (ATS) and European Respiratory Society (ERS), Japanese Respiratory Society (JRS), and the Latin American Thoracic Association (ALAT) (ref. 5 in main text). Non-diseased normal lung tissues were procured from lungs not used by the Northern California Transplant Donor Network. -
The Procollagen N-Proteinases ADAMTS2, 3 and 14 in Pathophysiology
Review The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology Mourad Bekhouche and Alain Colige Laboratory of Connective Tissues Biology, GIGA-R, University of Liège, B-4000 Sart Tilman, Belgium Correspondence to Alain Colige: Laboratory of Connective Tissues Biology, University of Liège, GIGA-Research, Tour de Pathologie B23/3, Avenue de l'Hôpital, 3, B-4000 Sart Tilman, Belgium. [email protected] http://dx.doi.org/10.1016/j.matbio.2015.04.001 Edited by W.C. Parks and S. Apte Abstract Collagen fibers are the main components of most of the extracellular matrices where they provide a structural support to cells, tissues and organs. Fibril-forming procollagens are synthetized as individual chains that associate to form homo- or hetero-trimers. They are characterized by the presence of a central triple helical domain flanked by amino and carboxy propeptides. Although there are some exceptions, these two propeptides have to be proteolytically removed to allow the almost spontaneous assembly of the trimers into collagen fibrils and fibers. While the carboxy-propeptide is mainly cleaved by proteinases from the tolloid family, the amino-propeptide is usually processed by procollagen N-proteinases: ADAMTS2, 3 and 14. This review summarizes the current knowledge concerning this subfamily of ADAMTS enzymes and discusses their potential involvement in physiopathological processes that are not directly linked to fibrillar procollagen processing. © 2015 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Introduction determine the cause of dermatosparaxis, a rare genetic disease that appeared in Belgian cattle herds during an Fibrillar collagens are the most abundant proteins inbreeding program [2,3]. -
Time-Series Plasma Cell-Free DNA Analysis Reveals Disease Severity of COVID-19 Patients
medRxiv preprint doi: https://doi.org/10.1101/2020.06.08.20124305; this version posted June 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Time-series plasma cell-free DNA analysis reveals disease severity of COVID- 19 patients Authors: Xinping Chen1†, Yu Lin2†, Tao Wu1†, Jinjin Xu2†, Zhichao Ma1†, Kun Sun2,5†, Hui Li1†, Yuxue Luo2,3†, Chen Zhang1, Fang Chen2, Jiao Wang1, Tingyu Kuo2,4, Xiaojuan Li1, Chunyu Geng2, Feng Lin1, Chaojie Huang2, Junjie Hu1, Jianhua Yin2, Ming Liu1, Ye Tao2, Jiye Zhang1, Rijing Ou2, Furong Xiao1, Huanming Yang2,6, Jian Wang2,6, Xun Xu2,7, Shengmiao Fu1*, Xin Jin2,3*, Hongyan Jiang1*, Ruoyan Chen2* Affiliations: 1Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Hainan Provincial Key Laboratory of Cell and Molecular Genetic Translational Medicine, Haikou 570311, Hainan, China. 2BGI-Shenzhen, Shenzhen, 518083, Guangdong, China 3School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, China 4BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, Guangdong, China 5Shenzhen Bay Laboratory, Shenzhen 518132, Guangdong, China 6James D. Watson Institute of Genome Sciences, Hangzhou 310058, China 7Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, 518120, China *Correspondence to: [email protected]; [email protected]; [email protected]; [email protected]. †These authors contributed equally to this work. Abstract: Clinical symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. -
Copper, Lysyl Oxidase, and Extracellular Matrix Protein Cross-Linking1–3
Copper, lysyl oxidase, and extracellular matrix protein cross-linking1–3 Robert B Rucker, Taru Kosonen, Michael S Clegg, Alyson E Mitchell, Brian R Rucker, Janet Y Uriu-Hare, and Carl L Keen Downloaded from https://academic.oup.com/ajcn/article/67/5/996S/4666210 by guest on 01 October 2021 ABSTRACT Protein-lysine 6-oxidase (lysyl oxidase) is a progress toward understanding copper’s role advanced quickly. cuproenzyme that is essential for stabilization of extracellular Lysyl oxidase is responsible for the formation of lysine-derived matrixes, specifically the enzymatic cross-linking of collagen and cross-links in connective tissue, particularly in collagen and elastin. A hypothesis is proposed that links dietary copper levels elastin. Normal cross-linking is essential in providing resistance to dynamic and proportional changes in lysyl oxidase activity in to elastolysis and collagenolysis by nonspecific proteinases, eg, connective tissue. Although nutritional copper status does not various proteinases involved in blood coagulation (11). Resis- influence the accumulation of lysyl oxidase as protein or lysyl tance to proteolysis occurs within a short period of copper reple- oxidase steady state messenger RNA concentrations, the direct tion in most animals; eg, Tinker et al (12) observed that the depo- influence of dietary copper on the functional activity of lysyl oxi- sition of aortic elastin is restored to near normal values after dase is clear. The hypothesis is based on the possibility that cop- 48–72 h of copper repletion in copper-deficient cockerels. per efflux and lysyl oxidase secretion from cells may share a Effects of copper deprivation are most pronounced in common pathway. -
Collagen Type XVIII (H-140): Sc-25720
SANTA CRUZ BIOTECHNOLOGY, INC. Collagen Type XVIII (H-140): sc-25720 The Power to Question BACKGROUND APPLICATIONS Type XV and XVIII collagens form the new subgroup MULTIPLEXIN, within the Collagen Type XVIII (H-140) is recommended for detection of Collagen α1 diverse family of collagens, which contains nineteen distinct types of collagens Type XVIII of mouse, rat and human origin by Western Blotting (starting found in vertebrates. Both type XV and XVIII collagens are characterized by dilution 1:200, dilution range 1:100-1:1000), immunoprecipitation [1–2 µg extensive interruptions in their collagenous sequences. Members of the MUL- per 100–500 µg of total protein (1 ml of cell lysate)] and immunofluores- TIPLEXIN subgroup contain polypeptides with multiple triple-helical domains cence (starting dilution 1:50, dilution range 1:50-1:500). separated and flanked by non-triple-helical regions. Type XV is predominantly Suitable for use as control antibody for Collagen Type XVIII siRNA (h): expressed in internal organs such as adrenal gland, kidney and pancreas. Type sc-43072 and Collagen Type XVIII siRNA (m): sc-43073. XVIII encodes two different α1 chains, which have different signal peptides and variant N-terminal non-collagenous NC1 domains of 495 and 303 amino Molecular Weight of Collagen Type XVIII: 20-22 kDa. acids. The long variant NC1-434 Type XVIII mRNAs are prominently expressed Positive Controls: rat C6 glioblastoma, human PBL or rat lung extract: sc-2396. in liver, while the variant NC1-303 mRNAs are predominantly expressed in heart, kidney, placenta, prostate, ovaries, skeletal muscle and small intestine. RECOMMENDED SECONDARY REAGENTS Endostatin is a fragment of the C-terminal domain NC1 of collagen XV and XVIII that inhibits angiogenesis and tumor growth. -
Gingival!Health!Transcriptome!
! ! ! Gingival!Health!Transcriptome! ! Thesis! ! Presented!in!Partial!Fulfillment!of!the!Requirements!for!the!Degree!Master!of! Science!in!the!Graduate!School!of!The!Ohio!State!University! ! By! Christina!Zachariadou,!DDS! Graduate!Program!in!Dentistry! The!Ohio!State!University! 2018! ! ! Thesis!Committee:! Angelo!J.!Mariotti,!DDS,!PhD,!Advisor! Thomas!C.!Hart,!DDS,!PhD! John!D.!Walters,!DDS,!MMSc! ! ! ! 1! ! ! ! ! ! ! ! ! ! ! Copyright!by! Christina!Zachariadou! 2018! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! 2! ! ! ! Abstract! ! Introduction:!In!the!field!of!periodontology,!a!satisfactory!definition!of!periodontal! health!is!lacking.!Instead,!clinicians!use!surrogate!measures,!such!as!color,!texture,! consistency,!probing!depths!and!bleeding!on!probing!to!examine!periodontal!tissues! and! diagnose! disease,! or! the! absence! of! it,! which! they! define! as! “clinical! health”.!! Additionally,!it!has!been!shown!that!age!progression!is!accompanied!by!changes!in! the!periodontium.!As!a!result,!understanding!the!gene!expression!in!healthy!gingiva,! through!the!field!of!transcriptomics,!could!provide!some!insight!on!the!molecules! that!contribute!to!gingival!health.!Also,!comparing!the!transcriptome!of!young!and! older!subjects,!taking!into!consideration!the!effect!of!sex/gender,!can!shed!light!on! differential! gene! expression! with! age! progression! and! on! individual! differences! between! sexes,! and! may! provide! future! therapeutic! endpoints! of! periodontal! treatment.!The!main!focus!of!this!study!was!to!ascertain!collagen!(COL)!and!matrix! -
Increased Endostatin/Collagen XVIII Expression Correlates with Elevated VEGF Level and Poor Prognosis in Hepatocellular Carcinoma
Modern Pathology (2005) 18, 663–672 & 2005 USCAP, Inc All rights reserved 0893-3952/05 $30.00 www.modernpathology.org Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma Tsung-Hui Hu1,*, Chao-Cheng Huang2,*, Chia-Ling Wu3, Pey-Ru Lin4, Shang-Yun Liu2, Jui-Wei Lin2, Jiin-Haur Chuang3 and Ming Hong Tai4,5 1Division of Hepatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Division of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 3Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan and 5Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan Liver is the primary source for collagen XVIII, the precursor of angiogenesis inhibitor, endostatin. However, the role of endostatin/collagen XVIII expression during liver carcinogenesis remains elusive. Therefore, we studied its expression in five hepatoma cell lines and 105 hepatocellular carcinoma specimens. The poorly differentiated hepatoma cell lines exhibited increased endostatin/collagen XVIII levels compared with the well-differentiated ones. In hepatoma tissues, endostatin/collagen XVIII expression was detected in various types of liver cells and was significantly stronger in adjacent nontumor tissues than that in tumors (Po0.001). Endostatin/collagen XVIII expression in nontumor tissues correlated with tumor stages (P ¼ 0.014) and expression of vascular endothelial growth factor (P ¼ 0.007), but not the stages of hepatic fibrosis (P40.05). Kaplan–Meier analysis showed that patients with higher endostatin/collagen XVIII expression had significantly shorter overall survival (P ¼ 0.011) and disease-free survival (P ¼ 0.0034).