Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappaB.
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.
Pubmed ID: 17626013 RIS Download
Activating Transcription Factor 2 | Adaptor Proteins, Signal Transducing | Cell Line, Transformed | Cell Transformation, Viral | Cyclic AMP Response Element-Binding Protein | Gene Products, tax | Humans | I-kappa B Kinase | MAP Kinase Kinase 4 | MAP Kinase Kinase Kinases | MAP Kinase Signaling System | NF-kappa B | Phosphorylation | Protein Processing, Post-Translational | T-Lymphocytes | p38 Mitogen-Activated Protein Kinases