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

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-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.

• Authors: Alpana Ray, Srijita Dhar, Arvind Shakya, Papiya Ray, Yasunori Okada, Bimal K Ray
• Journal: The FEBS journal (FEBS J) Vol. 276 Issue 15 Pg. 4276-86 (Aug 2009) ISSN: 1742-4658 [Electronic] England
• PMID: 19583771 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• DNA-Binding Proteins
• Proto-Oncogene Proteins c-myc
• Transcription Factors
• c-MYC-associated zinc finger protein

Topics

• Alternative Splicing
• Amino Acid Sequence
• Cell Line
• Chondrocytes (physiology)
• Cloning, Molecular
• DNA, Complementary (genetics)
• DNA-Binding Proteins (genetics)
• Gene Expression Regulation
• Gene Library
• Genetic Variation
• Humans
• Inflammation (genetics)
• Molecular Sequence Data
• Open Reading Frames
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-myc (genetics)
• Transcription Factors (genetics)