Constitutive activation of TAK1 by HTLV-1 TAX-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappa B

Authors:
Suzuki S, Singhirunnusorn P, Mori A, Yamaoka S, Kitajima I, Saiki I, Sakurai H
In:
Source: J Biol Chem
Publication Date: (2007)
Issue: 282(35): 25177-81
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
HuT 102
Species: human
Tissue Origin: blood
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
HTLV-1 Tax oncoprotein induces persistent activation of the transcription factor NF-kappaB and CREB (cAMP-response element-binding protein)/ATF. Transforming growth factor-beta-activated kinase 1 (TAK1) has been shown to play a critical role in these transcription factors. Here, we found that TAK1 was constitutively activated in Tax-positive HTLV-1-transformed T cells. Tax induced persistent overexpression of TAK1-binding protein 2 (TAB2), but not TAB3, which is essential for TAK1 activation. Surprisingly, TAK1 was not involved in the activation of NF-kappaB. On the other hand, JNK and p38 mitogen-activated protein kinases were activated by TAK1. In addition, ATF2, but not CREB, was a target for the TAK1-JNK pathway, and p38 negatively regulated TAK1 activity through TAB1 phosphorylation. These results indicate that Tax-mediated TAK1 activation is important for the activation of ATF2 rather than NF-kappaB.