Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

A new gamma-interferon-inducible promoter and splice variants of an anti-angiogenic human tRNA synthetase

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Liu, J. M.
  • Shue, E.
  • Ewalt, K. L.
  • Schimmel, Paul

publication date

  • January 2004

journal

  • Nucleic Acids Research  Journal

abstract

  • Two forms of human tryptophanyl-tRNA synthetase (TrpRS) are produced in vivo through alternative mRNA splicing. The two forms, full-length TrpRS and mini TrpRS, are catalytically active, but are distinguished by the striking anti-proliferative and anti-angiogenic activity specific to mini TrpRS. Here we describe two new splice variants of human TrpRS mRNA. Their production was strongly regulated by gamma-interferon (IFN-gamma), an anti-proliferative cytokine known to stimulate the expression of other anti-angiogenic factors. A new IFN-gamma-sensitive promoter was demonstrated to drive production of these splice variants. In human endothelial cells, both the newly discovered and a previously reported promoter were shown to respond specifically to IFN-gamma and not to other cytokines such as tumor necrosis factor-alpha, transforming growth factor-beta, interleukin-4 or erythropoietin. In addition, both promoters were stimulated by the 'downstream' interferon regulatory factor 1 that, in turn, is known to be regulated by the 'upstream' signal transducer and activator of transcription 1alpha subunit. Thus, the tandem promoters provide a dual system to regulate expression and alternative splicing of human TrpRS in vivo.

subject areas

  • 5' Untranslated Regions
  • Alternative Splicing
  • Angiogenesis Inhibitors
  • Base Sequence
  • Cells, Cultured
  • DNA-Binding Proteins
  • Endothelial Cells
  • Gene Expression Regulation, Enzymologic
  • HeLa Cells
  • Humans
  • Interferon Regulatory Factor-1
  • Interferon-gamma
  • Isoenzymes
  • Phosphoproteins
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Tryptophan-tRNA Ligase
scroll to property group menus

Identity

PubMed Central ID

  • PMC373357

International Standard Serial Number (ISSN)

  • 0305-1048

Digital Object Identifier (DOI)

  • 10.1093/nar/gkh240

PubMed ID

  • 14757836
scroll to property group menus

Additional Document Info

start page

  • 719

end page

  • 727

volume

  • 32

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support