HTLV-1 Tax-induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination.

Abstract:

:Human T-cell leukemia virus type 1 (HTLV-1) Tax-induced activation of nuclear factor-kappaB (NFkappaB) is thought to play a critical role in T-cell transformation and onset of adult T-cell leukemia. However, the molecular mechanism of the Tax-induced NFkappaB activation remains unknown. One of the mitogen-activated protein kinase kinase kinses (MAP3Ks) members, TAK1, plays a critical role in cytokine-induced activation of NFkappaB, which involves lysine 63-linked (K63) polyubiquitination of NEMO, a noncatalytic subunit of the IkappaB kinase complex. Here we show that Tax induces K63 polyubiquitination of NEMO. However, TAK1 is dispensable for Tax-induced NFkappaB activation, and deubiquitination of the K63 polyubiquitin chain failed to block Tax-induced NFkappaB activation. In addition, silencing of other MAP3Ks, including MEKK1, MEKK3, NIK, and TPL-2, did not affect Tax-induced NFkappaB activation. These results strongly suggest that unlike cytokine signaling, Tax-induced NFkappaB activation does not involve K63 polyubiquitination-mediated MAP3K activation.

authors

Gohda J,Irisawa M,Tanaka Y,Sato S,Ohtani K,Fujisawa J,Inoue J

doi

10.1016/j.bbrc.2007.03.125

subject

Has Abstract

pub_date

2007-05-25 00:00:00

pages

225-30

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)00611-0

journal_volume

357

pub_type

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