SAF-3, a novel splice variant of the SAF-1/MAZ/Pur-1 family, is expressed during inflammation

Alpana Ray, Srijita Dhar, Arvind Shakya, Papiya Ray, Yasunori Okada, Bimal K. Ray

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The Cys2His2-type zinc finger transcription factor serum amyloid A activating factor 1 [SAF-1, also known as MAZ (myc-associated zinc finger protein) or Pur-1 (purine binding factor-1)] plays an important role in regulation of a variety of inflammation-responsive genes. An SAF-2 splice variant acting as a negative regulator of SAF-1 was identified previously, and the present study reports the identification of a novel SAF-3 splice variant that is expressed during inflammation. SAF-3 mRNA, isolated from a cDNA library produced from IL-1β-induced cells, originates from a previously unknown first coding exon, and thereby contains a unique N-terminal domain but shares the same six zinc finger DNA-binding domains as present in SAF-1. In addition, a negatively functioning domain present at the N-terminus of SAF-1 and SAF-2 is spliced out in SAF-3. The expression of SAF-3 is very low in normal tissues and in cells grown under normal conditions. However, RT-PCR analysis of mRNAs from cytokine and growth factor-induced cells as well of mRNAs isolated from several diseased tissues revealed abundant expression of SAF-3. The transactivation potential of SAF-3 is much greater than that of the predominantly expressed splice variant SAF-1. These findings show that transcriptional regulation of downstream inflammation-responsive genes by SAF/MAZ/Pur-1 is likely to be more complex than previously assumed. In addition, we show that SAF-3 expression initiates from an upstream novel promoter. This is the first report of the existence of multiple promoters regulating expression of the SAF/MAZ/Pur-1 family of proteins.

Original languageEnglish
Pages (from-to)4276-4286
Number of pages11
JournalFEBS Journal
Volume276
Issue number15
DOIs
Publication statusPublished - 2009 Aug 1

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Keywords

  • Gene expression
  • Inflammation
  • SAF-1/MAZ/Pur-1
  • Splice variant
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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