DOCSLIB.ORG

ONCOGENOMICS Demonstrated to Be Highly Associated with Epstein-Barr Necrotic and Granulomatous Lesions in the Upper Virus (EBV) Infection (Harabuchi Et Al., 1990)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
ONCOGENOMICS Demonstrated to Be Highly Associated with Epstein-Barr Necrotic and Granulomatous Lesions in the Upper Virus (EBV) Infection (Harabuchi Et Al., 1990) Oncogene (2002) 21, 4702 – 4705 ª 2002 Nature Publishing Group All rights reserved 0950 – 9232/02 $25.00 www.nature.com/onc Frequent mutations of Fas gene in nasal NK/T cell lymphoma Tetsuya Takakuwa1, Zhiming Dong1, Shinichi Nakatsuka1, Shizuo Kojya2, Yasuaki Harabuchi3, Woo-Ick Yang5, Shigekazu Nagata4 and Katsuyuki Aozasa*,1 1Department of Pathology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; 2Department of Otorhinolaryngology, University of Ryukyus, Faculty of Medicine, Okinawa 903-0215, Japan; 3Department of Otorhinolaryngology, Asahikawa Medical College, Asahikawa 078-8510, Japan; 4Department of Genetics, Osaka University, Graduate School of Medicine, Osaka 565-0871, Japan; 5Department of Pathology, Yonsei University College of Medicine, Seoul, Korea Fas (Apo-1/CD95) is a cell-surface receptor involved in Fas (Apo-1/CD95) is a 45 kDa membrane protein cell death signaling through binding of Fas ligand. belonging to the tumor necrosis factor receptor family, Mutation of Fas gene in lymphoid cells results in and mediates programmed cell death (apoptosis) accumulation of these cells, which might thus contribute through binding of Fas ligand (FasL) (Suda et al., to lymphomagenesis. We examined the open reading 1993). Fas consists of 325 amino acids with a single frame of Fas cDNA in 14 cases of nasal NK/T-cell transmembrane domain, including signal peptide. The lymphoma. Mutations of Fas gene were detected in seven 80-amino acid portion in the cytoplasm, designated as a (50%) of 14 cases which comprised four frameshift, two death-signaling domain, is essential for the apoptotic missense, and one silent mutations. Frameshift mutations signal transduction (Itoh and Nagata, 1993). Fas gene were caused by insertion of 1 bp (A) at nucleotide 1095 mutations have been reported both in the lymphoid in two cases and by deletion of 1 bp at nucleotide 597 lineage and epithelial malignancies; about 10% of cases and at 704, respectively, in one each. Mouse T-cell with multiple myeloma (Landowski et al., 1997), 11% lymphoma cells transfected with two missense mutated with sporadic non-Hodgkin’s lymphoma (Gronbaek et genes and frameshift mutations caused by insertion of al., 1998), 20% with Hodgkin and Reed-Sternberg cells 1 bp (A) at nucleotide 1095 were resistant to apoptosis in classical Hodgkin’s disease (Muschen et al., 2000), induced by the anti-Fas antibody. These findings 11.6% with gastric cancer (Park et al., 2001), 7.7 – 20.3% suggested that accumulation of lymphoid cells with Fas with lung cancer (Lee et al., 1999b; Boldrini et al., 2001); mutations provides a basis for the development of nasal and 28% with urinary bladder cancer (Lee et al., 1999a). NK/T-cell lymphoma. Recent study showed that the nasal NKTCL Oncogene (2002) 21, 4702 – 4705. doi:10.1038/sj.onc. frequently express FasL together with Fas (Ng et al., 1205571 1999), which might be responsible for local tissue damage resulting in necrosis of tissue around tumors Keywords: nasal NK/T cell lymphoma; Fas; apoptosis; and contribute to the clinical aggressiveness of these mutation tumors. Alternatively, some mechanisms for resistance to Fas/FasL-induced apoptosis might work in the development of nasal NKTCL, thus Fas gene muta- tions could be one of the mechanisms for development Nasal NK/T-cell lymphoma (NKTCL) is a clinical of nasal NKTCL. Therefore, we examined the open condition of lethal midline granuloma that shows reading frame of Fas cDNA in 14 cases of nasal necrotic, granulomatous lesions in the upper respiratory NKTCL. Patients were admitted to the hospitals tract, especially in the nasal cavity (Jaffe et al., 1996). during the period from 1996 to 2000. Age of patients The disease is more frequent in Asian countries than in ranged from 36 to 82 years (median, 63) with a male to Western countries (Aozasa et al., 1992), and was female ratio of 11 : 3. All patients presented with the ONCOGENOMICS demonstrated to be highly associated with Epstein-Barr necrotic and granulomatous lesions in the upper virus (EBV) infection (Harabuchi et al., 1990). Recently, respiratory tract, mostly nasal cavity, which were mutations of c-kit proto-oncogene (Hongyo et al., 2000) biopsied for the histologic diagnosis before treatment. and tumor suppressor p53 gene (Li et al., 2000) were Histologic sections were reviewed by two of the reported. However, understanding of the molecular authors (T Takakuwa, K Aozasa) for diagnosis. mechanism of nasal NKTCL remained inadequate. Varying degrees of necrosis were found in the upper respiratory tract lesions. Diffuse proliferation of large atypical cells with mono- or multinucleus was observed accompanying with varying numbers of lymphocytes, *Correspondence: K Aozasa, Department of Pathology (C3), Osaka plasma cells, and macrophages, giving a polymorphous University Medical school, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan; E-mail: [email protected] appearance. An angiocentric pattern of proliferation Received 15 October 2001; revised 15 April 2002; accepted 15 April was occasionally observed. Immunohistochemically, 7 + + + 2002 tumor cells were CD20 , TIA-1 , CD16 , CD56 , Fas gene mutations in nasal lymphoma T Takakuwa et al 4703 CD3+,orCD43+. These histological and immunohis- nucleotide 1094. Two cases showed insertion of 1 bp tochemical findings were in agreement with those in the (A) at nucleotide 1095, which resulted in generation of nasal NKTCL (Jaffe et al., 1996). Denaturing gradient a frameshift. As a result, stop codon was introduced at gel electrophoresis analysis was employed to examine residue 304. Another case showed deletion of 1 bp (T) the rearrangement of the T-cell receptor g chain genes in a 7-(T) tract from nucleotide 591 to 597 of Fas in six of the present cases with proven clonal coding sequence. The remaining case had deletion of proliferation of EBV genome-containing cells, as 1 bp (C) at nucleotide 704. These two mutations previously described (Ohsawa et al., 1999). All six generated frameshifts, and resulted in stop codon at cases did not show clonally rearranged bands, residue 170. Because these mutants affect transmem- indicating the absence of T-cell clones in these cases. brane domain, the abnormal protein might not be RNA in situ hybridization using EBER-1 probe, which expressed on the cell surface. was performed as previously described (Weiss et al., Three point mutations were detected in exon 9, and 1992), revealed the positive signals in the nucleus of the two of these were missense ones, which caused proliferating cells in all cases, indicating the presence of substitutions of nonconserved amino acid. These EBV. mutations within the death domain affected codons Mutations of Fas gene were detected in seven (50%) 246 (ATC?GTC; Ile?Val) and 287 (CTT?CCT; of 14 cases of nasal NKTCL. Whether the detected Fas Leu?Pro) (GeneBank accession number M67454) mutations were heterozygous or homozygous could not (Itoh et al., 1991). be determined because nasal lesions showed a poly- Anti-human Fas antibody kills mouse T-cell lympho- morphous pattern of proliferation containing the ma cells WR19L which express human Fas cDNA. tumor cells and inflammatory reactive cells. The Fas This indicates that the Fas receptor mediates an mutations comprised of four frameshift, two missense, apoptotic signal into cells. To confirm whether the and one silent mutation (Figure 1). All but one of the mutations detected in the present cases abolish the silent mutations affected the death domain which is apoptotic signal transduction of the Fas receptor, these essential for apoptotic signal transduction. Previous Fas gene mutants were prepared and introduced into studies on the lymphoid lineage (Landowski et al., WR19L cells. Northern blot analysis demonstrated that 1997; Gronbaek et al., 1998; Muschen et al., 2000; Fas gene were expressed successfully (Figure 2a). Takakuwa et al., 2001) and epithelial malignancies (Lee However, fluorescence-activated cell sorting (FACS) et al., 1999a,b; Boldrini et al., 2001; Park et al., 2001) analysis with use of anti-Fas monoclonal antibody showed that the majority of Fas mutations observd in detected the expression of the human Fas receptor on these diseases were also located in the death domain. the cell surface only when Fas gene mutants containing Fas gene has a 6-(A) tract from nucleotide 1088 to a conserved transmembrane domain (A978G, 1095 ins A, T1102C) were introduced (Figure 2b). The ability of the mutated Fas on the cell surface to transduce the apoptotic signal was then examined in the established transformants. To exclude the clonal variations of Fas receptor expression, two independent clones were chosen for each mutant. Clones expressing the wild type Fas receptor were killed by Fas antibody. On the other hand, clones expressing the Fas receptor with any mutations (A978G, 1095 ins A, T1102C) were resistant to apoptosis induced by the anti-FAS anti- body (Figure 3). The NKTCL cells were reported to express Fas and FasL (Ng et al., 1999). Because cross-linking of FasL with Fas induces apoptosis, interaction of NKTCL cells from each other should result in apoptosis of the nasal NKTCL cells, thus prohibiting development of the disease. Therefore, some mechanism for resistance Figure 1 Summary of the Fas gene mutations found in patients of nasal NKTCL cells to Fas/FasL-induced apoptosis with nasal NKTCL. Total RNA was extracted using TRIzol re- might work for tumor development. Mutations of Fas agent (Gibco BRL, NY, USA) and was reverse-transcribed by gene could be one of the mechanisms. Mutations of random hexamer priming. The Fas open reading frame was am- Fas gene were detected in seven of 14 (50%) present plified using primer pairs of 5’-CACTTCGGAGGATTGCTCAA- cases of nasal NKTCL. Relatively high frequency of CA-3’ and 5’-TATGTTGGCTCTTC-AGCGCTA-3’ and then cloned in the pCR2.1-TOPO (Invitrogen, CA, USA). For the con- Fas gene mutations was reported in cases with thyroid trol of potential PCR error, eight to 12 clones derived from two lymphoma (65.4%) (Takakuwa et al., 2001) and other different PCR reactions were sequenced, respectively.
Load more

Recommended publications
  • The TNF and TNF Receptor Review Superfamilies: Integrating Mammalian Biology
    Cell, Vol. 104, 487±501, February 23, 2001, Copyright 2001 by Cell Press The TNF and TNF Receptor Review Superfamilies: Integrating Mammalian Biology Richard M. Locksley,*²³k Nigel Killeen,²k The receptors and ligands in this superfamily have and Michael J. Lenardo§k unique structural attributes that couple them directly to *Department of Medicine signaling pathways for cell proliferation, survival, and ² Department of Microbiology and Immunology differentiation. Thus, they have assumed prominent ³ Howard Hughes Medical Institute roles in the generation of tissues and transient microen- University of California, San Francisco vironments. Most TNF/TNFR SFPs are expressed in the San Francisco, California 94143 immune system, where their rapid and potent signaling § Laboratory of Immunology capabilities are crucial in coordinating the proliferation National Institute of Allergy and Infectious Diseases and protective functions of pathogen-reactive cells. National Institutes of Health Here, we review the organization of the TNF/TNFR SF Bethesda, Maryland 20892 and how these proteins have been adapted for pro- cesses as seemingly disparate as host defense and or- ganogenesis. In interpreting this large and highly active Introduction area of research, we have focused on common themes that unite the actions of these genes in different tissues. Three decades ago, lymphotoxin (LT) and tumor necro- We also discuss the evolutionary success of this super- sis factor (TNF) were identified as products of lympho- familyÐsuccess that we infer from its expansion across cytes and macrophages that caused the lysis of certain the mammalian genome and from its many indispens- types of cells, especially tumor cells (Granger et al., able roles in mammalian biology.
    [Show full text]
  • Pro- and Anti-Apoptotic CD95 Signaling in T Cells Maren Paulsen* and Ottmar Janssen
    Paulsen and Janssen Cell Communication and Signaling 2011, 9:7 http://www.biosignaling.com/content/9/1/7 DEBATE Open Access Pro- and anti-apoptotic CD95 signaling in T cells Maren Paulsen* and Ottmar Janssen Abstract The TNF receptor superfamily member CD95 (Fas, APO-1, TNFRSF6) is known as the prototypic death receptor in and outside the immune system. In fact, many mechanisms involved in apoptotic signaling cascades were solved by addressing consequences and pathways initiated by CD95 ligation in activated T cells or other “CD95-sensitive” cell populations. As an example, the binding of the inducible CD95 ligand (CD95L) to CD95 on activated T lymphocytes results in apoptotic cell death. This activation-induced cell death was implicated in the control of immune cell homeostasis and immune response termination. Over the past years, however, it became evident that CD95 acts as a dual function receptor that also exerts anti-apoptotic effects depending on the cellular context. Early observations of a potential non-apoptotic role of CD95 in the growth control of resting T cells were recently reconsidered and revealed quite unexpected findings regarding the costimulatory capacity of CD95 for primary T cell activation. It turned out that CD95 engagement modulates TCR/CD3-driven signal initiation in a dose- dependent manner. High doses of immobilized CD95 agonists or cellular CD95L almost completely silence T cells by blocking early TCR-induced signaling events. In contrast, under otherwise unchanged conditions, lower amounts of the same agonists dramatically augment TCR/CD3-driven activation and proliferation. In the present overview, we summarize these recent findings with a focus on the costimulatory capacity of CD95 in primary T cells and discuss potential implications for the T cell compartment and the interplay between T cells and CD95L-expressing cells including antigen-presenting cells.
    [Show full text]
  • A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-Cell Immunotherapy
    Published OnlineFirst December 17, 2020; DOI: 10.1158/2159-8290.CD-20-0756 RESEARCH BRIEF A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-cell Immunotherapy Ranjan Upadhyay1,2,3, Jonathan A. Boiarsky1,2,3, Gvantsa Pantsulaia1,2,3, Judit Svensson-Arvelund1,2,3, Matthew J. Lin1,2,3, Aleksandra Wroblewska2,3,4, Sherry Bhalla3,4, Nathalie Scholler5, Adrian Bot5, John M. Rossi5, Norah Sadek1,2,3, Samir Parekh1,2,3, Alessandro Lagana4, Alessia Baccarini2,3,4, Miriam Merad2,3,6, Brian D. Brown2,3,4, and Joshua D. Brody1,2,3 ABSTRACT T cell–based therapies have induced cancer remissions, though most tumors ulti- mately progress, reflecting inherent or acquired resistance including antigen Bianca Dunn by Illustration escape. Better understanding of how T cells eliminate tumors will help decipher resistance mecha- nisms. We used a CRISPR/Cas9 screen and identified a necessary role for Fas–FasL in antigen-specific T-cell killing. We also found that Fas–FasL mediated off-target “bystander” killing of antigen-negative tumor cells. This localized bystander cytotoxicity enhanced clearance of antigen-heterogeneous tumors in vivo, a finding that has not been shown previously. Fas-mediated on-target and bystander killing was reproduced in chimeric antigen receptor (CAR-T) and bispecific antibody T-cell models and was augmented by inhibiting regulators of Fas signaling. Tumoral FAS expression alone predicted survival of CAR-T–treated patients in a large clinical trial (NCT02348216). These data suggest strate- gies to prevent immune escape by targeting both the antigen expression of most tumor cells and the geography of antigen-loss variants.
    [Show full text]
  • CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30 And
    Published OnlineFirst August 7, 2018; DOI: 10.1158/2326-6066.CIR-18-0065 Research Article Cancer Immunology Research CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30þ and CD30– Embryonal Carcinoma via Antigen-Dependent and Fas/FasL Interactions Lee K. Hong1, Yuhui Chen2, Christof C. Smith1, Stephanie A. Montgomery3, Benjamin G. Vincent2, Gianpietro Dotti1,2, and Barbara Savoldo2,4 Abstract Tumor antigen heterogeneity limits success of chimeric (NSG) mouse model of metastatic EC. We observed that CD30. þ antigen receptor (CAR) T-cell therapies. Embryonal carcino- CAR T cells, while targeting CD30 EC tumor cells through mas (EC) and mixed testicular germ cell tumors (TGCT) the CAR (i.e., antigen-dependent targeting), also eliminated – containing EC, which are the most aggressive TGCT subtypes, surrounding CD30 EC cells in an antigen-independent man- are useful for dissecting this issue as ECs express the CD30 ner, via a cell–cell contact-dependent Fas/FasL interaction. In – þ – antigen but also contain CD30 /dim cells. We found that CD30- addition, ectopic Fas (CD95) expression in CD30 Fas EC was redirected CAR T cells (CD30.CAR T cells) exhibit antitumor sufficient to improve CD30.CAR T-cell antitumor activity. activity in vitro against the human EC cell lines Tera-1, Tera-2, Overall, these data suggest that CD30.CAR T cells might be and NCCIT and putative EC stem cells identified by Hoechst useful as an immunotherapy for ECs. Additionally, Fas/FasL dye staining. Cytolytic activity of CD30.CAR T cells was com- interaction between tumor cells and CAR T cells can be plemented by their sustained proliferation and proinflamma- exploited to reduce tumor escape due to heterogeneous antigen tory cytokine production.
    [Show full text]
  • Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy
    Hindawi Publishing Corporation ISRN Oncology Volume 2013, Article ID 371854, 25 pages http://dx.doi.org/10.1155/2013/371854 Review Article Targeting of the Tumor Necrosis Factor Receptor Superfamily for Cancer Immunotherapy Edwin Bremer Department of Surgery, Translational Surgical Oncology, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands Correspondence should be addressed to Edwin Bremer; [email protected] Received 10 April 2013; Accepted 11 May 2013 AcademicEditors:H.Al-Ali,J.Bentel,D.Canuti,L.Mutti,andR.V.Sionov Copyright © 2013 Edwin Bremer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The tumor necrosis factor (TNF) ligand and cognate TNF receptor superfamilies constitute an important regulatory axis that is pivotal for immune homeostasis and correct execution of immune responses. TNF ligands and receptors are involved in diverse biological processes ranging from the selective induction of cell death in potentially dangerous and superfluous cells to providing costimulatory signals that help mount an effective immune response. This diverse and important regulatory role in immunity has sparked great interest in the development of TNFL/TNFR-targeted cancer immunotherapeutics. In this review, I will discuss the biology of the most prominent proapoptotic and co-stimulatory TNF ligands and review their current status in cancer immunotherapy. 1. Introduction ligand/receptor interaction induces formation of a Death Inducing Signaling Complex (DISC) to the cytoplasmic DD The tumor necrosis factor (TNF) superfamily is comprised [3]. This DISC comprises the adaptor protein Fas-associated of 27 ligands that all share the hallmark extracellular TNF death domain (FADD) and an inactive proform of the homology domain (THD) [1].
    [Show full text]
  • Activation Cell Homeostasis in Chronic Immune Cutting Edge
    Cutting Edge: CD95 Maintains Effector T Cell Homeostasis in Chronic Immune Activation This information is current as Ramon Arens, Paul A. Baars, Margot Jak, Kiki Tesselaar, of September 24, 2021. Martin van der Valk, Marinus H. J. van Oers and René A. W. van Lier J Immunol 2005; 174:5915-5920; ; doi: 10.4049/jimmunol.174.10.5915 http://www.jimmunol.org/content/174/10/5915 Downloaded from References This article cites 30 articles, 9 of which you can access for free at: http://www.jimmunol.org/content/174/10/5915.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY CUTTING EDGE Cutting Edge: CD95 Maintains Effector T Cell Homeostasis in Chronic Immune Activation Ramon Arens,1*†‡ Paul A. Baars,* Margot Jak,* Kiki Tesselaar,* Martin van der Valk,§ Marinus H.
    [Show full text]
  • A Small Peptide Antagonist of the Fas Receptor Inhibits Neuroinflammation
    University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2019-09-30 A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma Anitha Krishnan Harvard Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Amino Acids, Peptides, and Proteins Commons, Biological Phenomena, Cell Phenomena, and Immunity Commons, Cell Biology Commons, Eye Diseases Commons, Nervous System Commons, Neuroscience and Neurobiology Commons, and the Ophthalmology Commons Repository Citation Krishnan A, Kocab AJ, Zacks DN, Marshak-Rothstein A, Gregory-Ksander M. (2019). A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma. Open Access Articles. https://doi.org/ 10.1186/s12974-019-1576-3. Retrieved from https://escholarship.umassmed.edu/oapubs/3987 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Krishnan et al. Journal of Neuroinflammation (2019) 16:184 https://doi.org/10.1186/s12974-019-1576-3 RESEARCH Open Access A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma Anitha Krishnan1, Andrew J.
    [Show full text]
  • Differential Regulation and Function of Fas Expression on Glial Cells Sung Joong Lee, Tong Zhou, Chulhee Choi, Zheng Wang and Etty N
    Differential Regulation and Function of Fas Expression on Glial Cells Sung Joong Lee, Tong Zhou, Chulhee Choi, Zheng Wang and Etty N. Benveniste This information is current as of September 28, 2021. J Immunol 2000; 164:1277-1285; ; doi: 10.4049/jimmunol.164.3.1277 http://www.jimmunol.org/content/164/3/1277 Downloaded from References This article cites 70 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/164/3/1277.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 28, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Differential Regulation and Function of Fas Expression on Glial Cells1 Sung Joong Lee,* Tong Zhou,† Chulhee Choi,* Zheng Wang,† and Etty N. Benveniste2* Fas/Apo-1 is a member of the TNF receptor superfamily that signals apoptotic cell death in susceptible target cells. Fas or Fas ligand (FasL)-deficient mice are relatively resistant to the induction of experimental allergic encephalomyelitis, implying the involvement of Fas/FasL in this disease process.
    [Show full text]
  • Human T Cells − CD27 + CD45RA + Effector-Type CD8 Activation
    Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27− Human T Cells This information is current as of September 29, 2021. Paul A. Baars, Laura M. Ribeiro do Couto, Jeanette H. W. Leusen, Berend Hooibrink, Taco W. Kuijpers, Susanne M. A. Lens and René A. W. van Lier J Immunol 2000; 165:1910-1917; ; doi: 10.4049/jimmunol.165.4.1910 Downloaded from http://www.jimmunol.org/content/165/4/1910 References This article cites 45 articles, 19 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/165/4/1910.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 29, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8؉CD45RA؉CD27؊ Human T Cells Paul A. Baars,1* Laura M.
    [Show full text]
  • 8 Death Receptor Mutations
    Chapter 8 / Death Receptor Mutations 149 8 Death Receptor Mutations Sug Hyung Lee, MD, PhD, Nam Jin Yoo, MD, PhD, and Jung Young Lee, MD, PhD, SUMMARY It is generally believed that human cancers may arise as the result of an accumulation of mutations in genes and subsequent clonal selection of variant progeny with increas- ingly aggressive behaviors. Also, among the remarkable advances in our understanding in cancer biology is the realization that apoptosis has a profound effect on the malignant phenotypes. Along with these, compelling evidence indicates that somatic mutations in the genes encoding apoptosis-related proteins contribute to either development or pro- gression of human cancers. In this chapter, we present an overview of the death receptor pathway and its dysregulation in cancers. We then review the current knowledge of death receptor mutations that have been detected in humans. INTRODUCTION Programmed cell death through apoptosis plays a fundamental role in a variety of physiological processes, and its deregulation contributes to many diseases, including autoimmunity, cancer, acquisition of drug resistance in tumors, stroke, progression of some degenerative diseases, and acquired immunodeficiency syndrome (AIDS) (1–4). Apoptosis is an active cell-suicide process executed by a cascade of molecular events involving a number of membrane receptors and cytoplasmic proteins (1–4). Although many pathways for activating caspases may exist, only two, the intrinsic pathway and the extrinsic pathway, have been demonstrated in detail (3). The extrinsic pathway can be induced by members of the tumor necrosis factor (TNF) receptor family, such as TNF receptor 1 (TNFR1) and Fas (5–7).
    [Show full text]
  • Death Receptors Couple to Both Cell Proliferation and Apoptosis
    Death receptors couple to both cell proliferation and apoptosis Ralph C. Budd J Clin Invest. 2002;109(4):437-442. https://doi.org/10.1172/JCI15077. Perspective No one will dispute that death receptors do exactly what their name suggests, induce programmed cell death. In addition, however, several reports have recently suggested that these receptors, or their downstream regulators, may also function in certain aspects of cell growth or differentiation. These claims might be met with justifiable skepticism. Certainly there is nothing more opposite in cell fate than growth and death. Yet the signal pathways used by these two processes appear to commingle, and the eventual outcome of the signaling vector may be bent toward one result over the other by seemingly subtle balances among these components. Here, following a brief review of the traditional signal pathways that lead from death receptor activation to apoptosis, I scrutinize the various reports of increased growth or differentiation mediated by these same receptors. I then consider newly identified signal pathways linked to death receptors that might promote growth and, finally, speculate on whether these events represent merely interesting in vitro manipulations or actual physiologically important processes. Conventional death receptor signaling The classical view of death receptor function is typified by Fas (CD95/APO-1), a member of the TNF receptor (TNFR) family (1). Trimerization, or more likely oligomerization of Fas, leads to formation of the death-inducing signal complex (DISC), starting with recruitment of the Fas-adapter protein FADD through their mutual death domains […] Find the latest version: https://jci.me/15077/pdf PERSPECTIVE SERIES Lymphocyte signal transduction Gary Koretzky, Series Editor Death receptors couple to both cell proliferation and apoptosis Ralph C.
    [Show full text]
  • Distinct Effects of CD30 and Fas Signaling in Cutaneous Anaplastic Lymphomas: a Possible Mechanism for Disease Progression
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Distinct Effects of CD30 and Fas Signaling in Cutaneous Anaplastic Lymphomas: A Possible Mechanism for Disease Progression Edi Levi, Zhenxi Wang, Tina Petrogiannis-Haliotis, Walther M. Pfeifer, Werner Kempf, Reed Drews, and Marshall E. Kadin Departments of Pathology and Medicine, Beth Israel-Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, U.S.A. Lymphomatoid papulosis is part of a spectrum of agonistic antibody, HeFi-1. Proliferative responses, CD30+ cutaneous lymphoproliferative disorders char- mitogen-activated protein kinase, and nuclear factor acterized by spontaneous tumor regression. The kB activities were determined with and without CD30 mechanism(s) of regression is unknown. In a recent activation. Mac-1 and Mac-2 A showed increased pro- study, a selective increase in CD30 ligand expression in liferative responses to incubation with CD30 activating regressing lesions of lymphomatoid papulosis and antibody, HeFi-1. Inhibition of the mitogen-activated cutaneous CD30+ anaplastic large cell lymphoma was protein kinase activity caused growth inhibition of the shown, suggesting that activation of the CD30 signal- Mac-1, Mac-2 A, and JK cell lines. Activation of the ing pathway may be responsible for tumor regression, Fas pathway induced apoptosis in all three cell lines. whereas no difference in Fas/Fas ligand expression Taken together, these ®ndings suggest that resistance was found between regressing and nonregressing to CD30-mediated growth inhibition provides a lesions. Therefore we tested the effects of CD30 and possible mechanism for escape of cutaneous anaplastic Fas activation on three CD30+ cutaneous lymphoma large cell lymphoma from tumor regression.
    [Show full text]