Bacillus anthracis lethal toxin represses MMTV promoter activity through transcription factors.
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.
Kang
Zhigang
Z
Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Room 4N13 (MSC 9401), Bethesda, MD 20892-9401, USA.
Webster Marketon
Jeanette I
JI
Johnson
Antoinette
A
Sternberg
Esther M
EM
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015533:Transcriptional Activation
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C030325:anthrax toxin; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate