A type I interferon signaling factor, ISF21, encoded on chromosome 21 is distinct from receptor components and their down-regulation and is necessary for transcriptional activation of interferon-regulated genes

Kerry A. Holland, Catherine M. Owczarek, Seung Y. Hwang, Martin J. Tymms, Stefan N. Constantinescu, Lawrence Pfeffer, Ismail Kola, Paul J. Hertzog

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The type I interferons (IFNs) are a family of cytokines, comprising at least 17 subtypes, which exert pleiotropic actions by interaction with a multi-component cell surface receptor and at least one well characterized signal transduction pathway involving JAK/STAT (Janus kinase/signal transducer and activator of transcription) proteins. In a previous report, we showed that a signaling factor, encoded by a gene located on the distal portion of chromosome 21, distinct from the IFNAR-1 receptor, was necessary for 2'-5'-oligoadenylate synthetase activity and antiviral responses, but not for high affinity ligand binding. In the present studies using hybrid Chinese hamster ovary cell lines containing portions of human chromosome 21, we show that the type I IFN signaling molecule, designated herein as ISF21, is distinct from the second receptor component, IFNAR-2, which is expressed in signaling and non-signaling cell lines. The location of the gene encoding ISF21 is narrowed to a region between the 10;21 and the r21 breakpoints, importantly eliminating the Mx gene located at 21q22.3 (the product of which is involved in IFN-induced antiviral responses) as a candidate for the signaling factor. To characterize the action of this factor in the type I IFN signaling pathway, we show that it acts independently of receptor down- regulation following ligand binding, both of which occur equally in the presence or absence of the factor. In addition, we demonstrate that ISF21 is necessary for transcriptional activation of 2'-5'-oligoadenylate synthetase, 6-16, and guanylate-binding protein gene promoter reporter constructs, which are mediated by several signaling pathways. ISF21 represents a novel factor as the localization to chromosome 21, and the data presented in this study exclude any of the known type I IFN signal-transducing molecules.

Original languageEnglish (US)
Pages (from-to)21045-21051
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number34
DOIs
StatePublished - Aug 22 1997

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Chromosomes, Human, Pair 21
Interferon Type I
Chromosomes
Interferons
Transcriptional Activation
Down-Regulation
Genes
Chemical activation
Ligases
Antiviral Agents
STAT Transcription Factors
Ligands
Janus Kinases
Cell Line
Cell Surface Receptors
Human Chromosomes
Cricetulus
Reporter Genes
Cells
Ovary

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A type I interferon signaling factor, ISF21, encoded on chromosome 21 is distinct from receptor components and their down-regulation and is necessary for transcriptional activation of interferon-regulated genes. / Holland, Kerry A.; Owczarek, Catherine M.; Hwang, Seung Y.; Tymms, Martin J.; Constantinescu, Stefan N.; Pfeffer, Lawrence; Kola, Ismail; Hertzog, Paul J.

In: Journal of Biological Chemistry, Vol. 272, No. 34, 22.08.1997, p. 21045-21051.

Research output: Contribution to journalArticle

Holland, Kerry A. ; Owczarek, Catherine M. ; Hwang, Seung Y. ; Tymms, Martin J. ; Constantinescu, Stefan N. ; Pfeffer, Lawrence ; Kola, Ismail ; Hertzog, Paul J. / A type I interferon signaling factor, ISF21, encoded on chromosome 21 is distinct from receptor components and their down-regulation and is necessary for transcriptional activation of interferon-regulated genes. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 34. pp. 21045-21051.
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T1 - A type I interferon signaling factor, ISF21, encoded on chromosome 21 is distinct from receptor components and their down-regulation and is necessary for transcriptional activation of interferon-regulated genes

AU - Holland, Kerry A.

AU - Owczarek, Catherine M.

AU - Hwang, Seung Y.

AU - Tymms, Martin J.

AU - Constantinescu, Stefan N.

AU - Pfeffer, Lawrence

AU - Kola, Ismail

AU - Hertzog, Paul J.

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AB - The type I interferons (IFNs) are a family of cytokines, comprising at least 17 subtypes, which exert pleiotropic actions by interaction with a multi-component cell surface receptor and at least one well characterized signal transduction pathway involving JAK/STAT (Janus kinase/signal transducer and activator of transcription) proteins. In a previous report, we showed that a signaling factor, encoded by a gene located on the distal portion of chromosome 21, distinct from the IFNAR-1 receptor, was necessary for 2'-5'-oligoadenylate synthetase activity and antiviral responses, but not for high affinity ligand binding. In the present studies using hybrid Chinese hamster ovary cell lines containing portions of human chromosome 21, we show that the type I IFN signaling molecule, designated herein as ISF21, is distinct from the second receptor component, IFNAR-2, which is expressed in signaling and non-signaling cell lines. The location of the gene encoding ISF21 is narrowed to a region between the 10;21 and the r21 breakpoints, importantly eliminating the Mx gene located at 21q22.3 (the product of which is involved in IFN-induced antiviral responses) as a candidate for the signaling factor. To characterize the action of this factor in the type I IFN signaling pathway, we show that it acts independently of receptor down- regulation following ligand binding, both of which occur equally in the presence or absence of the factor. In addition, we demonstrate that ISF21 is necessary for transcriptional activation of 2'-5'-oligoadenylate synthetase, 6-16, and guanylate-binding protein gene promoter reporter constructs, which are mediated by several signaling pathways. ISF21 represents a novel factor as the localization to chromosome 21, and the data presented in this study exclude any of the known type I IFN signal-transducing molecules.

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