Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-κB
Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-κB
复制标题
DOI：
10.1074/jbc.c700065200
复制
发表时间：
2007-08-31
影响因子：
4.8
通讯作者：
Sakurai, Hiroaki
中科院分区：
文献类型：
--
作者：
Suzuki, Shunsuke;Singhirunnusorn, Pattama;Sakurai, Hiroaki
HTLV-1 Tax癌蛋白诱导转录因子nf - κ B和camp反应元件结合蛋白(CREB)/ATF的持续激活。转化生长因子- β活化激酶1 （TAK1）已被证明在这些转录因子中起关键作用。在这里，我们发现TAK1在tax -阳性htlv -1转化的T细胞中被组成性激活。税收诱导TAK1结合蛋白2 （TAB2）的持续过表达，而不是TAB3，这是TAK1激活所必需的。令人惊讶的是，TAK1并没有参与NF-kappa b的激活。另一方面，JNK和p38丝裂原激活的蛋白激酶被TAK1激活。此外，ATF2，而不是CREB，是TAK1- jnk通路的靶标，p38通过TAB1磷酸化负调控TAK1活性。这些结果表明，税收介导的TAK1激活对ATF2的激活比nf - κ B的激活更重要。
HTLV-1 Tax oncoprotein induces persistent activation of the transcription factor NF-kappa B 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-kappa B. 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-kappa B.