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 language | English |
---|---|
Pages (from-to) | 4276-4286 |
Number of pages | 11 |
Journal | FEBS Journal |
Volume | 276 |
Issue number | 15 |
DOIs | |
Publication status | Published - 2009 Aug |
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Keywords
- Gene expression
- Inflammation
- SAF-1/MAZ/Pur-1
- Splice variant
- Transcription factor
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
SAF-3, a novel splice variant of the SAF-1/MAZ/Pur-1 family, is expressed during inflammation. / Ray, Alpana; Dhar, Srijita; Shakya, Arvind; Ray, Papiya; Okada, Yasunori; Ray, Bimal K.
In: FEBS Journal, Vol. 276, No. 15, 08.2009, p. 4276-4286.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SAF-3, a novel splice variant of the SAF-1/MAZ/Pur-1 family, is expressed during inflammation
AU - Ray, Alpana
AU - Dhar, Srijita
AU - Shakya, Arvind
AU - Ray, Papiya
AU - Okada, Yasunori
AU - Ray, Bimal K.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Gene expression
KW - Inflammation
KW - SAF-1/MAZ/Pur-1
KW - Splice variant
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=68149183280&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68149183280&partnerID=8YFLogxK
U2 - 10.1111/j.1742-4658.2009.07136.x
DO - 10.1111/j.1742-4658.2009.07136.x
M3 - Article
C2 - 19583771
AN - SCOPUS:68149183280
VL - 276
SP - 4276
EP - 4286
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 15
ER -