Bacillus anthracis lethal toxin represses MMTV promoter activity through transcription factors.
Bacillus anthracis lethal toxin represses MMTV promoter activity through transcription factors.
复制标题
炭疽杆菌致死毒素通过转录因子抑制 MMTV 启动子活性。
DOI：
10.1016/j.jmb.2009.04.030
复制
发表时间：
2009
影响因子：
5.6
通讯作者：
Sternberg,EstherM
中科院分区：
文献类型：
--
作者：
Kang,Zhigang;WebsterMarketon,JeanetteI;Johnson,Antoinette;Sternberg,EstherM
我们最近表明，炭疽致死毒素（LeTx）选择性抑制核激素受体。在这项研究中，我们发现，LeTx抑制激活的小鼠乳腺肿瘤病毒启动子相关的过度表达的转录因子肝细胞核因子3，八聚体结合蛋白1，和c-Jun。LeTx转录抑制与这些转录因子的蛋白水平的下降，在一个致命的因子蛋白酶活性依赖的方式。早期给予LeTx拮抗剂部分或完全消除了LeTx的抑制作用。与LeTx对丝裂原活化蛋白激酶激酶的快速裂解相反，这些转录因子的降解发生在LeTx处理后的相对晚期。此外，LeTx抑制佛波醇-12-肉豆蔻酸酯-13-乙酸酯诱导的小鼠乳腺肿瘤病毒启动子活性和佛波醇-12-肉豆蔻酸酯-13-乙酸酯诱导的内源性c-Jun蛋白。总的来说，这些研究结果表明，转录因子是LeTx的细胞内靶点，并扩大了我们对LeTx在低剂量暴露后期的分子作用的理解。
We have recently shown that the anthrax lethal toxin (LeTx) selectively represses nuclear hormone receptors. In this study, we found that LeTx repressed the activation of the mouse mammary tumor virus promoter related to overexpression of the transcription factors hepatocyte nuclear factor 3, octamer-binding protein 1, and c-Jun. LeTx transcriptional repression was associated with a decrease in the protein levels of these transcription factors in a lethal factor protease activity-dependent manner. Early administration of LeTx antagonists partially or completely abolished the repressive effects of LeTx. In contrast to the rapid cleavage of mitogen-activated protein kinase kinases by LeTx, the degradation of these transcription factors occurred at a relatively late stage after LeTx treatment. In addition, LeTx repressed phorbol-12-myristate-13-acetate-induced mouse mammary tumor virus promoter activity and phorbol 12-myristate 13-acetate induction of endogenous c-Jun protein. Collectively, these findings suggest that transcription factors are intracellular targets of LeTx and expand our understanding of the molecular action of LeTx at a later stage of low-dose exposure.