Gene promoter of apoptosis inhibitory protein IAP2

Identification of enhancer elements and activation by severe hypoxia

Zheng Dong, Junichiro Nishiyama, Xiaolan Yi, Manjeri A. Venkatachalam, Michael Denton, Sumin Gu, Senlin Li, Mei Qiang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 ≈ 3.5 kb was detected. We subsequently isolated 3.3 kb 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 ≈ 200 bp. 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.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalBiochemical Journal
Volume364
Issue number2
DOIs
StatePublished - Jun 1 2002

Fingerprint

Inhibitor of Apoptosis Proteins
Genes
Chemical activation
Apoptosis
Rats
Complementary DNA
Transcription
Transcriptional Activation
Hypoxia-Inducible Factor 1
Cyclic AMP Response Element-Binding Protein
Deferoxamine
Sequence Deletion
5' Flanking Region
Cell death
Genetic Promoter Regions
Gene expression
Cell Cycle
Proteins
Cell Death
Binding Sites

Keywords

  • Cell death
  • Gene regulation
  • Hypoxia-inducible factor-1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Gene promoter of apoptosis inhibitory protein IAP2 : Identification of enhancer elements and activation by severe hypoxia. / Dong, Zheng; Nishiyama, Junichiro; Yi, Xiaolan; Venkatachalam, Manjeri A.; Denton, Michael; Gu, Sumin; Li, Senlin; Qiang, Mei.

In: Biochemical Journal, Vol. 364, No. 2, 01.06.2002, p. 413-421.

Research output: Contribution to journalArticle

Dong, Zheng ; Nishiyama, Junichiro ; Yi, Xiaolan ; Venkatachalam, Manjeri A. ; Denton, Michael ; Gu, Sumin ; Li, Senlin ; Qiang, Mei. / Gene promoter of apoptosis inhibitory protein IAP2 : Identification of enhancer elements and activation by severe hypoxia. In: Biochemical Journal. 2002 ; Vol. 364, No. 2. pp. 413-421.
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AB - 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 ≈ 3.5 kb was detected. We subsequently isolated 3.3 kb 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 ≈ 200 bp. 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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