Replacement of 198MQMDII203 of mouse IRF-1 by 197IPVEVV202 of human IRF-1 abrogates induction of IFN-β, iNOS, and COX-2 gene expression by IRF-1

Meenakshi Upreti, Sanjiv Kumar, Pramod C. Rath

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Interferon regulatory factor-1 (IRF-1) is a transcription factor exhibiting functional diversity because of its ability to activate transcription from promoters of several IRF-1-dependent genes. It is a modular protein, where the overall structure is not essential for function of its individual domains. A comparison of the mouse and human IRF-1 amino acid sequences enabled us to identify a stretch of six amino acids (198-203) within the transactivation domain of mouse IRF-1, 198MQMDII203 to be different from that of the human IRF-1, 197IPVEVV 202. This indicated a possible functional significance of the six amino acid stretches in the two IRF-1 molecules. The murine IRF-1 sequence at 198-203 (MQMDII) was replaced by IPVEVV. Recombinant wild type mouse IRF-1 with 198MQMDII203 and its mutant form with 198IPVEVV203, expressed as GST-IRF-1-fusion proteins, showed similar DNA-binding activity. However, ectopic expression of the wild type and mutant IRF-1 in the human embryonic kidney (HEK-293) cells showed the effect of replacement of this region on expression of a few chromosomal genes that are transcriptionally activated by IRF-1 viz. IFN-β, iNOS, and COX-2 genes. In our study, expression of wild type IRF-1 activated these genes as judged by RT-PCR but the mutant IRF-1 did not show this effect. Thus, the MQMDII (198-203 a.a.) region of mouse IRF-1 has a functional context in relation to expression of IRF-1-inducible genes.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume314
Issue number3
DOIs
StatePublished - Feb 13 2004
Externally publishedYes

Keywords

  • COX-2
  • iNOS
  • Interferon-β
  • IRF-1
  • Transactivation domain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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