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PMID: 10535980 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

LFG: an anti-apoptotic gene that provides protection from Fas-mediated cell death.

Somia NV, Schmitt MJ, Vetter DE, Van Antwerp D, Heinemann SF, Verma IM

Abstract

Programmed cell death regulates a number of biological phenomena, and the apoptotic signal must itself be tightly controlled to avoid inappropriate cell death. We established a genetic screen to search for molecules that inhibit the apoptotic signal from the Fas receptor. Here we report the isolation of a gene, LFG, that protects cells uniquely from Fas but not from the mechanistically related tumor necrosis factor alpha death signal. LFG is widely distributed, but remarkably is highly expressed in the hippocampus. LFG can bind to the Fas receptor, but does not regulate Fas expression or interfere with binding of an agonist antibody. Furthermore LFG does not inhibit binding of FADD to Fas.

MeSH Terms
Amino Acid Sequence Antigens, CD/physiology Apoptosis/genetics Apoptosis Regulatory Proteins Base Sequence Blotting, Western Carrier Proteins/genetics Cell Line Cloning, Molecular DNA Primers Down-Regulation Fluorescent Antibody Technique HeLa Cells Humans Membrane Proteins Molecular Sequence Data Precipitin Tests Receptors, Tumor Necrosis Factor/physiology Receptors, Tumor Necrosis Factor, Type I Sequence Homology, Amino Acid fas Receptor/physiology
Chemicals
Antigens, CD Apoptosis Regulatory Proteins Carrier Proteins DNA Primers FAIM2 protein, human Membrane Proteins Receptors, Tumor Necrosis Factor Receptors, Tumor Necrosis Factor, Type I fas Receptor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Somia N V
The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Schmitt M J
Vetter D E
Van Antwerp D
Heinemann S F
Verma I M
References (50)
50 references, click to expand
  1. A matter of life and cell death.
    Science. 1998 Aug 28;281(5381):1317-22 PMID: 9721090
  2. DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies.
    Am J Pathol. 1998 May;152(5):1107-23 PMID: 9588877
  3. Inhibition of fas death signals by FLIPs.
    Curr Opin Immunol. 1998 Oct;10(5):552-8 PMID: 9794838
  4. Expression of fas antigen in the normal mouse brain.
    Biochem Biophys Res Commun. 1998 Nov 27;252(3):623-8 PMID: 9837756
  5. Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells.
    Immunity. 1998 Nov;9(5):711-20 PMID: 9846492
  6. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer.
    Nature. 1998 Dec 17;396(6712):699-703 PMID: 9872321
  7. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  8. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  9. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.
    J Exp Med. 1989 May 1;169(5):1747-56 PMID: 2469768
  10. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis.
    Cell. 1991 Jul 26;66(2):233-43 PMID: 1713127
  11. Cloning of cDNA for the glutamate-binding subunit of an NMDA receptor complex.
    Nature. 1991 Nov 7;354(6348):70-3 PMID: 1719427
  12. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen.
    J Biol Chem. 1992 May 25;267(15):10709-15 PMID: 1375228
  13. A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen.
    J Biol Chem. 1993 May 25;268(15):10932-7 PMID: 7684370
  14. Identification and characterization of a cDNA encoding mouse CAP: a homolog of the yeast adenylyl cyclase associated protein.
    J Cell Sci. 1993 Jul;105 ( Pt 3):777-85 PMID: 7691848
  15. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family.
    Cell. 1993 Dec 17;75(6):1169-78 PMID: 7505205
  16. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule.
    Science. 1994 Mar 25;263(5154):1759-62 PMID: 7510905
  17. The putative Drosophila NMDARA1 gene is located on the second chromosome and is ubiquitously expressed in embryogenesis.
    Biochim Biophys Acta. 1995 Apr 4;1261(2):301-3 PMID: 7711078
  18. A novel protein that interacts with the death domain of Fas/APO1 contains a sequence motif related to the death domain.
    J Biol Chem. 1995 Apr 7;270(14):7795-8 PMID: 7536190
  19. Involvement of an ICE-like protease in Fas-mediated apoptosis.
    Nature. 1995 May 4;375(6526):78-81 PMID: 7536900
  20. FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis.
    Cell. 1995 May 19;81(4):505-12 PMID: 7538907
  21. Identification of a novel conserved human gene, TEGT.
    Genomics. 1995 Jul 20;28(2):301-4 PMID: 8530040
  22. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.
    J Exp Med. 1995 Nov 1;182(5):1545-56 PMID: 7595224
  23. Neural membrane protein 35 (NMP35): a novel member of a gene family which is highly expressed in the adult nervous system.
    Mol Cell Neurosci. 1998 Aug;11(5-6):260-73 PMID: 9698393
  24. The adenovirus E3/10.4K-14.5K proteins down-modulate the apoptosis receptor Fas/Apo-1 by inducing its internalization.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10072-7 PMID: 9707602
  25. Death receptors: signaling and modulation.
    Science. 1998 Aug 28;281(5381):1305-8 PMID: 9721089
  26. Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver.
    Nat Genet. 1995 Nov;11(3):294-300 PMID: 7581453
  27. WEHI-13VAR: a stable and sensitive variant of WEHI 164 clone 13 fibrosarcoma for tumor necrosis factor bioassay.
    Immunol Lett. 1995 May;46(1-2):107-10 PMID: 7590904
  28. Identification and characterization of a new member of the TNF family that induces apoptosis.
    Immunity. 1995 Dec;3(6):673-82 PMID: 8777713
  29. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
    Cell. 1996 Jun 14;85(6):803-15 PMID: 8681376
  30. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
    Cell. 1996 Jun 14;85(6):817-27 PMID: 8681377
  31. Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14486-91 PMID: 8962078
  32. Programmed cell death in animal development.
    Cell. 1997 Feb 7;88(3):347-54 PMID: 9039261
  33. Apoptosis by death factor.
    Cell. 1997 Feb 7;88(3):355-65 PMID: 9039262
  34. Cell death in the regulation of immune responses.
    Curr Opin Immunol. 1997 Jun;9(3):365-70 PMID: 9203410
  35. Casper is a FADD- and caspase-related inducer of apoptosis.
    Immunity. 1997 Jun;6(6):751-63 PMID: 9208847
  36. Inhibition of death receptor signals by cellular FLIP.
    Nature. 1997 Jul 10;388(6638):190-5 PMID: 9217161
  37. I-FLICE, a novel inhibitor of tumor necrosis factor receptor-1- and CD-95-induced apoptosis.
    J Biol Chem. 1997 Jul 11;272(28):17255-7 PMID: 9211860
  38. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.
    J Biol Chem. 1997 Jul 25;272(30):18542-5 PMID: 9228018
  39. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  40. FISH identifies different types of duplications with 12q13-15 as the commonly involved segment in B-cell lymphoproliferative malignancies characterized by partial trisomy 12.
    Genes Chromosomes Cancer. 1997 Oct;20(2):155-66 PMID: 9331566
  41. Gene transfer of Fas ligand induces tumor regression in vivo.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13862-7 PMID: 9391118
  42. Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer's disease.
    J Neurol Sci. 1997 Nov 6;152(1):73-83 PMID: 9395128
  43. Identification of new translocation breakpoints at 12q13 in lipomas.
    Genomics. 1997 Nov 15;46(1):70-7 PMID: 9403060
  44. An induced proximity model for caspase-8 activation.
    J Biol Chem. 1998 Jan 30;273(5):2926-30 PMID: 9446604
  45. Interaction of the adenovirus 14.7-kDa protein with FLICE inhibits Fas ligand-induced apoptosis.
    J Biol Chem. 1998 Mar 6;273(10):5815-20 PMID: 9488717
  46. Co-expression of Fas and Fas ligand in malignant glial tumors and cell lines.
    Acta Neuropathol. 1998 Mar;95(3):287-90 PMID: 9542594
  47. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases.
    EMBO J. 1998 Apr 15;17(8):2215-23 PMID: 9545235
  48. Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells.
    Nature. 1998 Apr 16;392(6677):726-30 PMID: 9565035
  49. Toso, a cell surface, specific regulator of Fas-induced apoptosis in T cells.
    Immunity. 1998 Apr;8(4):461-71 PMID: 9586636
  50. Persistent expression of Fas/FasL mRNA in the mouse hippocampus after a single NMDA injection.
    J Neurochem. 1998 Oct;71(4):1773-6 PMID: 9751215
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-10-26
Pages
12667-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23041
Subset
IM
Grants
NIA NIH HHS · AG10435 · United States
NCI NIH HHS · CA44360 · United States
NIA NIH HHS · P01 AG010435 · United States
NHLBI NIH HHS · R01 HL053670 · United States
NHLBI NIH HHS · HL3670 · United States
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