Constitutive activity of the tumor necrosis factor promoter is canceled by the 3′ untranslated region in nonmacrophage cell lines; A trans-dominant factor overcomes this suppressive effect

Veronique Kruys, Kathleen Kemmer, Alexander Shakhov, Victor Jongeneel, Bruch Beutler

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58 Citations (Scopus)

Abstract

The role of the mouse tumor necrosis factor (TNF) promoter, 5′ untranslated region (UTR), and 3′ UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in all three cell lines. Not only the full-length promoter but also truncated versions of the promoter, lacking NF-κB binding motifs, are active in each type of cell. The TNF 3′ UTR effectively cancels reporter gene expression in HeLa cells and in NIH 3T3 cells but fails to block expression in L-929 cells. L-929 cells contain a factor that overcomes the inhibitory influence of the TNF 3′ UTR. Its action depends upon the presence of sequences found in the TNF 5′ UTR. Cell-fusion experiments reveal that this activator is trans-dominant. These studies highlight the essential role played by the TNF 3′ UTR, which silences the TNF gene in cells that might otherwise express TNF. They also reveal the existence of an escape mechanism whereby inappropriate synthesis of TNF might occur.

Original languageEnglish (US)
Pages (from-to)673-677
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number2
StatePublished - 1992

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3' Untranslated Regions
Tumor Necrosis Factor-alpha
Cell Line
5' Untranslated Regions
Reporter Genes
Gene Expression
NIH 3T3 Cells
Cell Fusion
HeLa Cells
Macrophages

Keywords

  • Cytokine
  • Posttranscriptional regulation
  • Transactivator
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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abstract = "The role of the mouse tumor necrosis factor (TNF) promoter, 5′ untranslated region (UTR), and 3′ UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in all three cell lines. Not only the full-length promoter but also truncated versions of the promoter, lacking NF-κB binding motifs, are active in each type of cell. The TNF 3′ UTR effectively cancels reporter gene expression in HeLa cells and in NIH 3T3 cells but fails to block expression in L-929 cells. L-929 cells contain a factor that overcomes the inhibitory influence of the TNF 3′ UTR. Its action depends upon the presence of sequences found in the TNF 5′ UTR. Cell-fusion experiments reveal that this activator is trans-dominant. These studies highlight the essential role played by the TNF 3′ UTR, which silences the TNF gene in cells that might otherwise express TNF. They also reveal the existence of an escape mechanism whereby inappropriate synthesis of TNF might occur.",
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year = "1992",
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T1 - Constitutive activity of the tumor necrosis factor promoter is canceled by the 3′ untranslated region in nonmacrophage cell lines; A trans-dominant factor overcomes this suppressive effect

AU - Kruys, Veronique

AU - Kemmer, Kathleen

AU - Shakhov, Alexander

AU - Jongeneel, Victor

AU - Beutler, Bruch

PY - 1992

Y1 - 1992

N2 - The role of the mouse tumor necrosis factor (TNF) promoter, 5′ untranslated region (UTR), and 3′ UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in all three cell lines. Not only the full-length promoter but also truncated versions of the promoter, lacking NF-κB binding motifs, are active in each type of cell. The TNF 3′ UTR effectively cancels reporter gene expression in HeLa cells and in NIH 3T3 cells but fails to block expression in L-929 cells. L-929 cells contain a factor that overcomes the inhibitory influence of the TNF 3′ UTR. Its action depends upon the presence of sequences found in the TNF 5′ UTR. Cell-fusion experiments reveal that this activator is trans-dominant. These studies highlight the essential role played by the TNF 3′ UTR, which silences the TNF gene in cells that might otherwise express TNF. They also reveal the existence of an escape mechanism whereby inappropriate synthesis of TNF might occur.

AB - The role of the mouse tumor necrosis factor (TNF) promoter, 5′ untranslated region (UTR), and 3′ UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in all three cell lines. Not only the full-length promoter but also truncated versions of the promoter, lacking NF-κB binding motifs, are active in each type of cell. The TNF 3′ UTR effectively cancels reporter gene expression in HeLa cells and in NIH 3T3 cells but fails to block expression in L-929 cells. L-929 cells contain a factor that overcomes the inhibitory influence of the TNF 3′ UTR. Its action depends upon the presence of sequences found in the TNF 5′ UTR. Cell-fusion experiments reveal that this activator is trans-dominant. These studies highlight the essential role played by the TNF 3′ UTR, which silences the TNF gene in cells that might otherwise express TNF. They also reveal the existence of an escape mechanism whereby inappropriate synthesis of TNF might occur.

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KW - Posttranscriptional regulation

KW - Transactivator

KW - Transcription

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