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

Research output: Contribution to journalArticle

105 Citations (Scopus)

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

Fingerprint

Inhibitor of Apoptosis Proteins
Tumor Necrosis Factor-alpha
Genes
5' Flanking Region
Transcription
Binding Sites
Interferon Regulatory Factor-1
NFATC Transcription Factors
Electrophoretic mobility
Tumor Necrosis Factor Receptors
Transcription Factor AP-1
Response Elements
Electrophoretic Mobility Shift Assay
Luciferases
Interleukin-1
Genetic Promoter Regions
Transcriptional Activation
Glucocorticoids
Epstein-Barr virus EBV-associated membrane antigen
Assays

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{1648de15f0114d97946a7bc1ca192f7b,
title = "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",
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.",
author = "Hong, {Sang Yong} and Yoon, {Wan Hee} and Park, {Ji Hyun} and Kang, {Seung Goo} and Ahn, {Jin Hyung} and Lee, {Tae Ho}",
year = "2000",
month = "6",
day = "16",
doi = "10.1074/jbc.M001202200",
language = "English",
volume = "275",
pages = "18022--18028",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "24",

}

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

In: Journal of Biological Chemistry, Vol. 275, No. 24, 16.06.2000, p. 18022-18028.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Hong, Sang Yong

AU - Yoon, Wan Hee

AU - Park, Ji Hyun

AU - Kang, Seung Goo

AU - Ahn, Jin Hyung

AU - Lee, Tae Ho

PY - 2000/6/16

Y1 - 2000/6/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034674737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034674737&partnerID=8YFLogxK

U2 - 10.1074/jbc.M001202200

DO - 10.1074/jbc.M001202200

M3 - Article

C2 - 10751398

AN - SCOPUS:0034674737

VL - 275

SP - 18022

EP - 18028

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 24

ER -