SAF-3, a novel splice variant of the SAF-1/MAZ/Pur-1 family, is expressed during inflammation.
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-1beta-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.
Ray
Alpana
A
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA. rayb@missouri.edu
Dhar
Srijita
S
Shakya
Arvind
A
Ray
Papiya
P
Okada
Yasunori
Y
Ray
Bimal K
BK
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002460:Cell Line; D019902:Chondrocytes / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D015723:Gene Library; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein