Small GTP-Binding Protein Ran Is Regulated by Posttranslational
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
XPO1E571K Mutation Modifies Exportin 1 Localisation And
cancers Article XPO1E571K Mutation Modifies Exportin 1 Localisation and Interactome in B-Cell Lymphoma Hadjer Miloudi 1, Élodie Bohers 1,2, François Guillonneau 3 , Antoine Taly 4,5 , Vincent Cabaud Gibouin 6,7 , Pierre-Julien Viailly 1,2 , Gaëtan Jego 6,7 , Luca Grumolato 8 , Fabrice Jardin 1,2 and Brigitte Sola 1,* 1 INSERM U1245, Unicaen, Normandie University, F-14000 Caen, France; [email protected] (H.M.); [email protected] (E.B.); [email protected] (P.-J.V.); [email protected] (F.J.) 2 Centre de lutte contre le Cancer Henri Becquerel, F-76000 Rouen, France 3 Plateforme Protéomique 3P5, Université de Paris, Institut Cochin, INSERM, CNRS, F-75014 Paris, France; [email protected] 4 Laboratoire de Biochimie Théorique, CNRS UPR 9030, Université de Paris, F-75005 Paris, France; [email protected] 5 Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, PSL Research University, F-75005 Paris, France 6 INSERM, LNC UMR1231, F-21000 Dijon, France; [email protected] (V.C.G.); [email protected] (G.J.) 7 Team HSP-Pathies, University of Burgundy and Franche-Comtée, F-21000 Dijon, France 8 INSERM U1239, Unirouen, Normandie University, F-76130 Mont-Saint-Aignan, France; [email protected] * Correspondence: [email protected]; Tel.: +33-2-3156-8210 Received: 11 September 2020; Accepted: 28 September 2020; Published: 30 September 2020 Simple Summary: Almost 25% of patients with either primary mediastinal B-cell lymphoma (PMBL) or classical Hodgkin lymphoma (cHL) possess a recurrent mutation of the XPO1 gene encoding the major nuclear export protein. -
Plant Rangaps Are Localized at the Nuclear Envelope in Interphase and Associated with Microtubules in Mitotic Cells
The Plant Journal (2002) 30(6), 699±709 Plant RanGAPs are localized at the nuclear envelope in interphase and associated with microtubules in mitotic cells Aniko Pay1, Katja Resch2, Hanns Frohnmeyer2, Erzsebet Fejes1, Ferenc Nagy1 and Peter Nick2,* 1Plant Biology Institute, Biological Research Center, H-6701 Szeged, PO Box 521, Hungary, and 2Institut fuÈr Biologie II/Botanik, SchaÈnzlestrasse 1, UniversitaÈt Freiburg, D-79104 Freiburg, Germany Received 17 December 2001; revised 7 March 2002; accepted 15 March 2002. *For correspondence (fax +49 761 203 2612; e-mail [email protected]). Summary In animals and yeast, the small GTP-binding protein Ran has multiple functions ± it is involved in mediating (i) the directional passage of proteins and RNA through the nuclear pores in interphase cells; and (ii) the formation of spindle asters, the polymerization of microtubules, and the re-assembly of the nuclear envelope in mitotic cells. Nucleotide binding of Ran is modulated by a series of accessory proteins. For instance, the hydrolysis of RanGTP requires stimulation by the RanGTPase protein RanGAP. Here we report the complementation of the yeast RanGAP mutant rna1 with Medicago sativa and Arabidopsis thaliana cDNAs encoding RanGAP-like proteins. Confocal laser microscopy of Arabidopsis plants overexpressing chimeric constructs of GFP with AtRanGAP1 and 2 demonstrated that the fusion protein is localized to patchy areas at the nuclear envelope of interphase cells. In contrast, the cellular distribution of RanGAPs in synchronized tobacco cells undergoing mitosis is characteristically different. Double-immuno¯uorescence shows that RanGAPs are co-localized with spindle microtubules during anaphase, with the microtubular phragmoplast and the surface of the daughter nuclei during telophase. -
UNIVERSITY of CALIFORNIA, SAN DIEGO Functional Analysis of Sall4
UNIVERSITY OF CALIFORNIA, SAN DIEGO Functional analysis of Sall4 in modulating embryonic stem cell fate A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Molecular Pathology by Pei Jen A. Lee Committee in charge: Professor Steven Briggs, Chair Professor Geoff Rosenfeld, Co-Chair Professor Alexander Hoffmann Professor Randall Johnson Professor Mark Mercola 2009 Copyright Pei Jen A. Lee, 2009 All rights reserved. The dissertation of Pei Jen A. Lee is approved, and it is acceptable in quality and form for publication on microfilm and electronically: ______________________________________________________________ ______________________________________________________________ ______________________________________________________________ ______________________________________________________________ Co-Chair ______________________________________________________________ Chair University of California, San Diego 2009 iii Dedicated to my parents, my brother ,and my husband for their love and support iv Table of Contents Signature Page……………………………………………………………………….…iii Dedication…...…………………………………………………………………………..iv Table of Contents……………………………………………………………………….v List of Figures…………………………………………………………………………...vi List of Tables………………………………………………….………………………...ix Curriculum vitae…………………………………………………………………………x Acknowledgement………………………………………………….……….……..…...xi Abstract………………………………………………………………..…………….....xiii Chapter 1 Introduction ..…………………………………………………………………………….1 Chapter 2 Materials and Methods……………………………………………………………..…12 -
Cselp Functions As the Nuclear Export Receptor for Importin a in Yeast
FEBS 20654 FEBS Letters 433 (1998) 185 190 Cselp functions as the nuclear export receptor for importin a in yeast Markus Kfinzler, Eduard C. Hurt* Biochemie-Zentrum Heidelberg ( BZH), Ruprecht-Karls-Universitgit, lm Neuenheimer Feld 328, 4. OG, 69120 Heidelberg, Germany Received 14 May 1998; revised version' received 14 July 1998 review see [4,5]). The similarity is mainly found in a Ran-GTP Abstract CSEI is essential for yeast cell viability and has been implicated in chromosome segregation. Based on its sequence bindirfg domain at the N-terminus of these proteins [8,9]. similarity, Cselp has been grouped into the family of importin Binding of Ran-GTP has opposite effects on the binding of like nucleocytoplasmic transport receptors with highest homol- cargo by import and export receptors. Complexes between ogy to the recently identified human nuclear export receptor for import receptors and cargo are dissociated by Ran-GTP, importin ~, CAS. We demonstrate here that Cselp physically whereas binding of Ran-GTP and cargo to export receptors interacts with yeast Ran and yeast importin tx (Srplp) in the is cooperative. These properties of import and export recep- yeast two-hybrid system and that recombinant Cselp, Srplp and tors together with a high concentration of Ran-GTP in the Ran-GTP form a trimeric complex in vitro. Re-export of Srplp nucleus trigger release of cargo from import receptors and from the nucleus into the cytoplasm and nuclear uptake of a association of cargo with export receptors in the nucleus. Re- reporter protein containing a classical NLS are inhibited in a lease of export cargo and binding of import cargo in the csel mutant strain. -
T-Cell Protein Tyrosine Phosphatase Attenuates STAT3 and Insulin
ORIGINAL ARTICLE T-Cell Protein Tyrosine Phosphatase Attenuates STAT3 and Insulin Signaling in the Liver to Regulate Gluconeogenesis Atsushi Fukushima,1 Kim Loh,1 Sandra Galic,1 Barbara Fam,2 Ben Shields,1 Florian Wiede,1 Michel L. Tremblay,3 Matthew J. Watt,4 Sofianos Andrikopoulos,2 and Tony Tiganis1 OBJECTIVE—Insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt signaling and interleukin-6 (IL-6)-instigated JAK/ STAT3-signaling pathways in the liver inhibit the expression of ype 2 diabetes has reached epidemic propor- gluconeogenic genes to decrease hepatic glucose output. The tions, afflicting roughly 170 million people world- insulin receptor (IR) and JAK1 tyrosine kinases and STAT3 can wide. Although the underlying genetic causes serve as direct substrates for the T-cell protein tyrosine phos- Tand the associated pathologic symptoms are phatase (TCPTP). Homozygous TCPTP-deficiency results in peri- heterogenous, a common feature is high blood glucose due natal lethality prohibiting any informative assessment of to peripheral insulin resistance. Circulating insulin re- TCPTP’s role in glucose homeostasis. Here we have used leased from -cells in the pancreas serves to lower blood Ptpn2ϩ/Ϫ mice to investigate TCPTP’s function in glucose glucose by triggering the translocation of the facilitative homeostasis. GLUT4 to the plasma membrane in muscle and adipose RESEARCH DESIGN AND METHODS—We analyzed insulin tissue (1). Insulin also acts in the liver to promote glycogen sensitivity and gluconeogenesis in chow versus high-fat–fed synthesis and lipogenesis and to suppress hepatic glucose (HFF) Ptpn2ϩ/Ϫ and Ptpn2ϩ/ϩ mice and insulin and IL-6 production (HGP) by inhibiting gluconeogenesis and gly- signaling and gluconeogenic gene expression in Ptpn2ϩ/Ϫ and cogenolysis (1). -
Download the Abstract Book
1 Exploring the male-induced female reproduction of Schistosoma mansoni in a novel medium Jipeng Wang1, Rui Chen1, James Collins1 1) UT Southwestern Medical Center. Schistosomiasis is a neglected tropical disease caused by schistosome parasites that infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs, yet our understanding of their sexual reproduction is limited because egg production is not sustained for more than a few days in vitro. Here, we explore the process of male-stimulated female maturation in our newly developed ABC169 medium and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. By performing an RNAi screen for genes whose expression was enriched in the female reproductive organs, we identify a single nuclear hormone receptor that is required for differentiation and maturation of germ line stem cells in female gonad. Furthermore, we screen genes in non-reproductive tissues that maybe involved in mediating cell signaling during the male-female interplay and identify a transcription factor gli1 whose knockdown prevents male worms from inducing the female sexual maturation while having no effect on male:female pairing. Using RNA-seq, we characterize the gene expression changes of male worms after gli1 knockdown as well as the female transcriptomic changes after pairing with gli1-knockdown males. We are currently exploring the downstream genes of this transcription factor that may mediate the male stimulus associated with pairing. -
Sirt7 Promotes Adipogenesis in the Mouse by Inhibiting Autocatalytic
Sirt7 promotes adipogenesis in the mouse by inhibiting PNAS PLUS autocatalytic activation of Sirt1 Jian Fanga,1, Alessandro Iannia,1, Christian Smolkaa,b, Olesya Vakhrushevaa,c, Hendrik Noltea,d, Marcus Krügera,d, Astrid Wietelmanna, Nicolas G. Simonete, Juan M. Adrian-Segarraa, Alejandro Vaqueroe, Thomas Brauna,2, and Eva Bobera,2 aDepartment of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, D-61231 Bad Nauheim, Germany; bMedizin III Kardiologie und Angiologie, Universitätsklinikum Freiburg, D-79106 Freiburg, Germany; cDepartment of Medicine, Hematology/Oncology, Goethe University, D-60595 Frankfurt am Main, Germany; dInstitute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), D-50931 Köln, Germany; and eCancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Barcelona, Catalonia, Spain Edited by C. Ronald Kahn, Section of Integrative Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, and approved August 23, 2017 (received for review April 26, 2017) Sirtuins (Sirt1–Sirt7) are NAD+-dependent protein deacetylases/ adipogenesis and accumulation of lipids in 3T3-L1 adipocytes by ADP ribosyltransferases, which play decisive roles in chromatin deacetylation of FOXO1, which represses PPARγ (10). The role of silencing, cell cycle regulation, cellular differentiation, and metab- Sirt6 in the regulation of adipogenic differentiation is less clear olism. Different sirtuins control similar cellular processes, suggest- although it is known that Sirt6 knockout (KO) mice suffer from ing a coordinated mode of action but information about potential reduced adipose tissue stores, while Sirt6 overexpressing mice cross-regulatory interactions within the sirtuin family is still lim- are protected against high-fat diet-induced obesity (11, 12). -
Goat Anti-RCBTB2 Antibody Size: 100Μg Specific Antibody in 200Μl
EB09067 - Goat Anti-RCBTB2 Antibody Size: 100µg specific antibody in 200µl Target Protein Principal Names: RCBTB2, regulator of chromosome condensation (RCC1) and BTB (POZ) domain containing protein 2, CHC1L, OTTHUMP00000018399, RCC1-like G UK Office exchanging factor RLG, chromosome condensation 1-like, regulator of chromosome condensation and BTB domain containing protein 2 Everest Biotech Ltd Official Symbol: RCBTB2 Cherwell Innovation Centre Accession Number(s): NP_001259.1 77 Heyford Park Human GeneID(s): 1102 Upper Heyford Non-Human GeneID(s): 105670 (mouse), 290363 (rat) Oxfordshire Important Comments: This antibody is not expected to cross-react with RCBTB1. OX25 5HD UK Immunogen Peptide with sequence CEHFRSSLEDNEDD, from the internal region of the protein Enquiries: sequence according to NP_001259.1. [email protected] Sales: Please note the peptide is available for sale. [email protected] Tech support: Purification and Storage [email protected] Purified from goat serum by ammonium sulphate precipitation followed by antigen affinity chromatography using the immunizing peptide. Tel: +44 (0)1869 238326 Supplied at 0.5 mg/ml in Tris saline, 0.02% sodium azide, pH7.3 with 0.5% bovine serum Fax: +44 (0)1869 238327 albumin. Aliquot and store at -20°C. Minimize freezing and thawing. US Office Everest Biotech c/o Abcore Applications Tested 405 Maple Street, Suite A106 Peptide ELISA: antibody detection limit dilution 1:2000. Ramona, Western blot: Preliminary experiments gave an approx. 30kDa band in Human Liver, CA 92065 Lung and Tonsil lysates after 1µg/ml antibody staining. Please note that currently we USA cannot find an explanation in the literature for the band we observe given the calculated size of 60.3kDa according to NP_001259.1. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Rangap1 Induces Gtpase Activity of Nuclear Ras-Related Ran (Gtpase-Activating Protein/Rccl/TC4/G2 Checkpoint) F
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 2587-2591, March 1994 Biochemistry RanGAP1 induces GTPase activity of nuclear Ras-related Ran (GTPase-activating protein/RCCl/TC4/G2 checkpoint) F. RALF BISCHOFF*t, CHRISTIAN KLEBEt, JURGEN KRETSCHMER*, ALFRED WITrINGHOFERt, AND HERWIG PONSTINGL* *Division for Molecular Biology of Mitosis, German Cancer Research Center, D-69120 Heidelberg, Federal Republic of Germany; and *Abteilung Strukturelle Biologie, Max-Planck-Institut ffr Molekulare Physiologie, D-44139 Dortmund, Federal Republic of Germany Communicated by Hans Neurath, December 3, 1993 ABSTRACT The nuclear Ras-related protein Ran binds DMAE-650/M (Merck; Superformance, 26 x 115 mm) in 20 guanine nucleotide and is involved in cell cycle regulation. mM Bis-Tris-propane HCl, pH 7.0/1 mM DTT with a linear Models of the signal pathway predict Ran to be active as gradient of NaCl from 0.05 M to 1 M at a flow rate of 5 Ran GTP at the initiation of S phase upon activation by the ml/min. Fractions containing RanGAP were pooled and nucleotide exchange factor RCC1 and to be inactivated for the immediately applied to a hydroxylapatite column (Merck; onset of mitosis by hydrolysis of bound GTP. Here a nuclear Superformance, 10 x 150 mm) in 20 mM potassium phos- homodimeric 65-kDa protein, RanGAPl, is described, which phate, pH 7.0/1 mM DTT, with a linear gradient from 20 mM we believe to be the immediate antagonist of RCC1. It was to 1 M phosphate at a flow rate of 2 ml/min. To fractions purified from HeLa cell lysates and induces GTPase activity of containing RanGAP, ammonium sulfate in 20 mM Bis-Tris- Ran, but not Ras, by more than 3 orders of magnitude. -
Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002) -
(KPNA7), a Divergent Member of the Importin a Family of Nuclear Import
Kelley et al. BMC Cell Biology 2010, 11:63 http://www.biomedcentral.com/1471-2121/11/63 RESEARCH ARTICLE Open Access Karyopherin a7 (KPNA7), a divergent member of the importin a family of nuclear import receptors Joshua B Kelley1, Ashley M Talley1, Adam Spencer1, Daniel Gioeli2, Bryce M Paschal1,3* Abstract Background: Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin a and importin b. NLS cargo is recognized by importin a, which is bound by importin b. Importin b mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin b triggers disassembly of the complex. To date, six importin a family members, encoded by separate genes, have been described in humans. Results: We sequenced and characterized a seventh member of the importin a family of transport factors, karyopherin a 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin b (IBB) is divergent, and shows stronger binding to importin b than the IBB domains from of other importin a family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. Conclusion: KPNA7 is a novel importin a family member in humans that belongs to the importin a2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin a family.