Suzuki Shunsuke, Singhirunnusorn Pattama, Mori Akinori, Yamaoka Shoji, Kitajima Isao, Saiki Ikuo, Sakurai Hiroaki
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
J Biol Chem. 2007 Aug 31;282(35):25177-81. doi: 10.1074/jbc.C700065200. Epub 2007 Jul 11.
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.
人嗜T淋巴细胞病毒1型（HTLV-1）的Tax癌蛋白可诱导转录因子核因子κB（NF-κB）和环磷酸腺苷反应元件结合蛋白（CREB）/活化转录因子（ATF）的持续激活。转化生长因子β激活激酶1（TAK1）已被证明在这些转录因子中起关键作用。在此，我们发现TAK1在Tax阳性的HTLV-1转化T细胞中持续激活。Tax诱导TAK1结合蛋白2（TAB2）而非TAB3的持续过表达，而TAB2是TAK1激活所必需的。令人惊讶的是，TAK1不参与NF-κB的激活。另一方面，JNK和p38丝裂原活化蛋白激酶被TAK1激活。此外，ATF2而非CREB是TAK1-JNK途径的作用靶点，并且p38通过TAB1磷酸化负向调节TAK1活性。这些结果表明，Tax介导的TAK1激活对ATF2的激活而非NF-κB的激活很重要。
