Inhibitors of apoptosis (IAPs) antagonize cell death and regulate the cell cycle. One mechanism controlling IAP expression is translation initiation through the internal ribosome entry sites. Alternatively, IAP expression can be regulated at the transcription level. We showed recently the activation of IAP2 transcription by severe hypoxia. To pursue this regulation, we have cloned the full-length cDNA of rat IAP2, and have isolated and analysed the promoter regions of this gene. The cDNA encodes a protein of 589 amino acids, exhibiting structural features of IAP. In rat tissues, a major IAP2 transcript of ≈3.5kb was detected. We subsequently isolated 3.3kb of the proximal 5′-flanking regions of this gene, which showed significant promoter activity. Of interest, 5′ sequential deletion of the promoter sequence identified an enhancer of ≈200bp. Deletion of cAMP-response-element-binding protein (CREB) sites in the enhancer sequence diminished its activity. Finally, the IAP2 gene promoter was activated significantly by severe hypoxia and not by CoCl2 or desferrioxamine, pharmacological inducers of hypoxia-inducible factor-1. In conclusion, in this study we have cloned the full-length cDNA of rat IAP2, and for the first time we have isolated and analysed promoter sequences of this gene, leading to the identification of enhancer elements. Moreover, we have demonstrated activation of the gene promoter by severe hypoxia, a condition shown to induce IAP2. These findings provide a basis for further investigation of gene regulation of IAP2, a protein with multiple functions.
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June 2002
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Research Article|
June 01 2002
Gene promoter of apoptosis inhibitory protein IAP2: identification of enhancer elements and activation by severe hypoxia
Zheng DONG;
Zheng DONG
1
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
1To whom correspondence should be addressed (e-mail dong@uthscsa.edu).
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Junichiro NISHIYAMA;
Junichiro NISHIYAMA
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Xiaolan YI;
Xiaolan YI
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Manjeri A. VENKATACHALAM;
Manjeri A. VENKATACHALAM
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Michael DENTON;
Michael DENTON
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Sumin GU;
Sumin GU
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Senlin LI;
Senlin LI
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Mei QIANG
Mei QIANG
Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, U.S.A.
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Publisher: Portland Press Ltd
Received:
October 05 2001
Revision Received:
February 06 2002
Accepted:
March 15 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 364 (2): 413–421.
Article history
Received:
October 05 2001
Revision Received:
February 06 2002
Accepted:
March 15 2002
Citation
Zheng DONG, Junichiro NISHIYAMA, Xiaolan YI, Manjeri A. VENKATACHALAM, Michael DENTON, Sumin GU, Senlin LI, Mei QIANG; Gene promoter of apoptosis inhibitory protein IAP2: identification of enhancer elements and activation by severe hypoxia. Biochem J 1 June 2002; 364 (2): 413–421. doi: https://doi.org/10.1042/bj20011431
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