Activation of NF-κB/Rel by Tax involves degradation of IκBα and is blocked by a proteasome inhibitor

S. B. Maggirwar, Edward Harhaj, S. C. Sun

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The tax gene product of the human T-cell leukemia virus type I(HTLV-I) induces the nuclear expression and biological function of the NF-κB/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-κB/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway. Transient transfection and reporter gene assays have revealed that Tax overrides the inhibitory function of IκBα in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of IκBα requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of IκBα, which is also required for tumor necrosis factor alpha-induced degradation of this inhibitory protein. We further demonstrate that the proteasome inhibitor also blocks the degradation of IκBα observed in HTLV-I-infected T cells. Interestingly, inhibition of IκBα degradation in these cells led to the accumulation of a phosphorylated form of IκBα. Together, these studies suggest that Tax activation of NF-κB/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor IκBα.

Original languageEnglish (US)
Pages (from-to)993-998
Number of pages6
JournalOncogene
Volume11
Issue number5
StatePublished - Jan 1 1995

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Proteasome Inhibitors
T-Lymphocytes
Human T-lymphotropic virus 1
Jurkat Cells
Proteasome Endopeptidase Complex
Reporter Genes
Proteolysis
Transfection
Amino Acid Sequence
Transcription Factors
Tumor Necrosis Factor-alpha
Phosphorylation
Amino Acids
Human T-lymphotrophic virus 1 tax protein

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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title = "Activation of NF-κB/Rel by Tax involves degradation of IκBα and is blocked by a proteasome inhibitor",
abstract = "The tax gene product of the human T-cell leukemia virus type I(HTLV-I) induces the nuclear expression and biological function of the NF-κB/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-κB/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway. Transient transfection and reporter gene assays have revealed that Tax overrides the inhibitory function of IκBα in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of IκBα requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of IκBα, which is also required for tumor necrosis factor alpha-induced degradation of this inhibitory protein. We further demonstrate that the proteasome inhibitor also blocks the degradation of IκBα observed in HTLV-I-infected T cells. Interestingly, inhibition of IκBα degradation in these cells led to the accumulation of a phosphorylated form of IκBα. Together, these studies suggest that Tax activation of NF-κB/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor IκBα.",
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Activation of NF-κB/Rel by Tax involves degradation of IκBα and is blocked by a proteasome inhibitor. / Maggirwar, S. B.; Harhaj, Edward; Sun, S. C.

In: Oncogene, Vol. 11, No. 5, 01.01.1995, p. 993-998.

Research output: Contribution to journalArticle

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N2 - The tax gene product of the human T-cell leukemia virus type I(HTLV-I) induces the nuclear expression and biological function of the NF-κB/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-κB/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway. Transient transfection and reporter gene assays have revealed that Tax overrides the inhibitory function of IκBα in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of IκBα requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of IκBα, which is also required for tumor necrosis factor alpha-induced degradation of this inhibitory protein. We further demonstrate that the proteasome inhibitor also blocks the degradation of IκBα observed in HTLV-I-infected T cells. Interestingly, inhibition of IκBα degradation in these cells led to the accumulation of a phosphorylated form of IκBα. Together, these studies suggest that Tax activation of NF-κB/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor IκBα.

AB - The tax gene product of the human T-cell leukemia virus type I(HTLV-I) induces the nuclear expression and biological function of the NF-κB/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-κB/Rel can be inhibited by a proteasome inhibitor, suggesting the involvement of proteolytic reactions in this Tax-specific activation pathway. Transient transfection and reporter gene assays have revealed that Tax overrides the inhibitory function of IκBα in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of IκBα requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of IκBα, which is also required for tumor necrosis factor alpha-induced degradation of this inhibitory protein. We further demonstrate that the proteasome inhibitor also blocks the degradation of IκBα observed in HTLV-I-infected T cells. Interestingly, inhibition of IκBα degradation in these cells led to the accumulation of a phosphorylated form of IκBα. Together, these studies suggest that Tax activation of NF-κB/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor IκBα.

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