Activation of NF-kappa B/Rel by Tax involves degradation of I kappa B alpha 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-kappa B/Rel family of host transcription factors although the underlying mechanism remains unclear. In the present study, we demonstrate that Tax-mediated activation of NF-kappa B/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 I kappa B alpha in both F9 embryonal cells and Jurkat T cells. Moreover, Tax-mediated inactivation of I kappa B alpha requires a 16 amino acid sequence element located at the N-terminal region (amino acid 21-36) of I kappa B alpha, 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 I kappa B alpha observed in HTLV-I-infected T cells. Interestingly, inhibition of I kappa B alpha degradation in these cells led to the accumulation of a phosphorylated form of I kappa B alpha. Together, these studies suggest that Tax activation of NF-kappa B/Rel may involve induction of phosphorylation and subsequent proteasome-mediated degradation of the inhibitor I kappa B alpha.

journal_name

Oncogene

journal_title

Oncogene

authors

Maggirwar SB,Harhaj E,Sun SC

subject

Has Abstract

pub_date

1995-09-07 00:00:00

pages

993-8

issue

5

eissn

0950-9232

issn

1476-5594

journal_volume

11

pub_type

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