SAF-2, a splice variant of SAF-1, acts as a negative regulator of transcription.
Serum amyloid A-activating factor-1 (SAF-1), a Cys(2)His(2)-type zinc finger transcription factor, regulates inflammation-induced expression of serum amyloid A protein that is linked to the pathogenesis of reactive amyloidosis, rheumatoid arthritis, and atherosclerosis. Here we report the identification of a novel splice variant, SAF-2, of the SAF family bearing strong sequence similarity to SAF-1. The N-terminal 426 amino acids of both SAF-1 and SAF-2 are identical containing two polyalanine tracts, one proline-rich domain, and six zinc fingers. However, the C terminus of SAF-2 containing two additional zinc fingers is different from SAF-1, which indicates the capability of different biochemical function. We show that SAF-2 interacts more avidly with the SAF-binding element, but its transactivation potential is much lower than SAF-1. Furthermore, co-expression of SAF-2 markedly suppresses SAF-1-regulated promoter function. Finally, we show that the level of SAF-2 protein is reduced during many inflammatory conditions, whereas the SAF-1 protein level remains unchanged. Together, these data suggest that the relative abundance of SAF-2 plays a critical role in the fine tuned regulation of inflammation-responsive genes that are controlled by SAF-1.
Ray
Bimal K
BK
Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri 65211. rayb@missouri.edu
Murphy
Ryan
R
Ray
Papiya
P
Ray
Alpana
A
D001483:Base Sequence; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein