Identification of the distinct promoters for the two transcripts of apoptosis related protein 3 and their transcriptional regulation by NFAT and NFκB

Department of Biochemistry and Molecular Biology, State Key Lab of Cancer Biology, Fourth Military Medical University, Xi'an 710032, P.R. China.
Molecular and Cellular Biochemistry (Impact Factor: 2.39). 09/2007; 302(1-2):187-94. DOI: 10.1007/s11010-007-9440-7
Source: PubMed


APR3 (apoptosis related protein 3) is a novel gene highly conserved across species. Analysis of the data about APR3 available at GEO profiles revealed consistent and significant changes of APR3 expression level in certain developmental and inflammatory processes. Based on the search and analysis of all the submitted mRNA sequence, we postulated that the two transcripts may arise from separate promoter activities rather than previously assumed alternative splicing. Through reporter assay and PCR data, we identified the distinct promoters for the two transcripts of APR3. Furthermore, exogenous expression of a constitutively active mutant of transcription factor NFAT was able to enhance both the promoter activities of APR3. Sequential deletion of the promoter from the 5' side and mutation of the promoter suggested the functional NFAT binding sites might localize between -96 bp and -47 bp. In contrast, exogenous expression of a constitutively active mutant of the transcription factor NFkB inhibited APR3 transcription. Our data suggested that APR3 might be functionally important in certain processes under which NFAT and/or NFkappaB are/is activated.

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    • "NF-κB is considered the “master” gene transcription factor for promoting inflammation by regulating proinflammatory mediators. On the other hand, NF-κB itself is activated by these same inflammatory cytokines [32, 33]. Studies in mouse models show that NF-κB and TNF-α are linked with cancer progression [34, 35]. "
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