Involvement of two NF-κB binding elements in tumor necrosis factor α-, CD40-, and Epstein-Barr virus latent membrane protein 1-mediated induction of the cellular inhibitor of apoptosis protein 2 gene

Sang Yong Hong, Wan Hee Yoon, Ji Hyun Park, Seung Goo Kang, Jin Hyung Ahn, Tae Ho Lee

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Abstract

The antiapoptotic function of NF-κB is believed to be mediated through the induction of antiapoptotic genes. Among the antiapoptotic genes, cellular inhibitor of apoptosis protein 2 (c-IAP2/HIAP-1/MIHC) is originally identified as a molecule recruited to the tumor necrosis factor (TNF) receptor complex, and its expression is preferentially up-regulated by TNF and other stimuli activating NF-κB. However, direct evidence of transcriptional regulation of NF-κB on the c-IAP2 gene is still missing. Here, we have cloned and characterized the promoter region required for NF- κB-dependent transcription of the c-IAP2 gene. Sequencing of a 3.5-kilobase fragment of the 5'-flanking region of the c-IAP2 gene has identified a TATA- like sequence and potential binding sites for nuclear factor of activated T cells, interferon regulatory factor 1, activator protein 1, glucocorticoid response element, and three putative NF-κB binding elements. Deletion and mutational analysis of the 5'-flanking region linked to the luciferase gene revealed that transcriptional activation by TNF or interleukin 1 is mediated cooperatively by two NF-κB binding sites. Electrophoretic mobility shift assays characterized that the two NF-κB sites can be recognized and bound by the NF-κB p50/p65 heterodimer. In addition, the transcription of c-IAP2 promoter was strongly up-regulated when CD40 or Epstein-Barr virus latent membrane protein 1 was overexpressed.

Original languageEnglish
Pages (from-to)18022-18028
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number24
DOIs
Publication statusPublished - 2000 Jun 16

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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