The interferon consensus sequence-binding protein (ICSBP/IRF8) represses PTPN13 gene transcription in differentiating myeloid cells

The Journal of Biological Chemistry
Weiqi HuangElizabeth A Eklund

Abstract

The interferon consensus sequence-binding protein (ICSBP/IRF8) is an interferon regulatory factor that is expressed in myeloid and B-cells. ICSBP-deficient mice develop a myeloproliferative disorder characterized by cytokine hypersensitivity and apoptosis resistance. To identify ICSBP target genes involved in these effects, we screened a CpG island microarray with chromatin that co-immunoprecipitated with ICSBP from myeloid cells. Using this technique, we identified PTPN13 as an ICSBP target gene. PTPN13 encodes Fas-associated phosphatase 1 (Fap-1), a ubiquitously expressed protein-tyrosine phosphatase. This was of interest because interaction of Fap-1 with Fas results in Fas dephosphorylation and inhibition of Fas-induced apoptosis. In this study, we found that ICSBP influenced Fas-induced apoptosis in a Fap-1-dependent manner. We also found that ICSBP interacted with a cis element in the proximal PTPN13 promoter and repressed transcription. This interaction increased during myeloid differentiation and was regulated by phosphorylation of conserved tyrosine residues in the interferon regulatory factor domain of ICSBP. ICSBP deficiency was present in human myeloid malignancies, including chronic myeloid leukemia. Therefore, thes...Continue Reading

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Citations

Jan 6, 2010·Cancer Immunology, Immunotherapy : CII·David SavitskyTadatsugu Taniguchi
Apr 8, 2011·The Journal of Biological Chemistry·Ling BeiElizabeth Eklund
Aug 9, 2013·The Journal of Clinical Investigation·Liping HuElizabeth A Eklund
Sep 28, 2012·Beilstein Journal of Organic Chemistry·Gehad Zeyat, Karola Rück-Braun
Oct 10, 2009·Leukemia & Lymphoma·Jessica Koenigsmann, Dirk Carstanjen
Jul 29, 2008·Biochemical Pharmacology·Geoffrey GloireJacques Piette
Dec 2, 2010·British Journal of Haematology·Rolf Marschalek
Dec 18, 2012·Oncoimmunology·Hideyuki YanaiTadatsugu Taniguchi
Jul 6, 2016·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Scott I AbramsMichelle N Messmer
May 5, 2018·American Journal of Respiratory and Critical Care Medicine·Alison BambergDavid W H Riches
Oct 1, 2017·Cold Spring Harbor Perspectives in Biology·Hideo NegishiHideyuki Yanai
Jan 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alessandra FragaleAngela Battistini
Sep 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jine YangKebin Liu
Dec 17, 2020·Biomolecules·Soha McheikGilles Freiss

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