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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activating Transcription Factor 2 / metabolism*
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Adaptor Proteins, Signal Transducing / metabolism*
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Cell Line, Transformed
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Cell Transformation, Viral*
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Cyclic AMP Response Element-Binding Protein / metabolism
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Gene Products, tax / metabolism*
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Humans
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I-kappa B Kinase / metabolism
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MAP Kinase Kinase 4 / metabolism
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MAP Kinase Kinase Kinases / metabolism*
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MAP Kinase Signaling System*
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NF-kappa B / metabolism
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Phosphorylation
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Protein Processing, Post-Translational*
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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ATF2 protein, human
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Activating Transcription Factor 2
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Adaptor Proteins, Signal Transducing
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CREB1 protein, human
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Cyclic AMP Response Element-Binding Protein
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Gene Products, tax
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NF-kappa B
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TAB2 protein, human
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I-kappa B Kinase
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinases
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MAP kinase kinase kinase 7
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MAP Kinase Kinase 4