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)
|