Novel Repression of the Glucocorticoid Receptor by Anthrax Lethal Toxin

Authors

  • JEANETTE I. WEBSTER,

    1. Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, Bethesda, Maryland 20892, USA
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  • MAHTAB MOAYERI,

    1. National Institute of Autoimmune and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
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  • ESTHER M. STERNBERG

    Corresponding author
    1. Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, Bethesda, Maryland 20892, USA
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Address for correspondence: Esther M. Sternberg, M.D., Section on Neuroendocrine Immunology and Behavior, NIMH, NIH, Bldg. 36, Rm. 1A23, 36 Convent Drive, MSC 4020, Bethesda, MD 20892-4020.Voice: +1 301-402-2773; fax: +1 301-496-6095. sternbee@mail.nih.gov

Abstract

Abstract: Death from anthrax has been reported to occur from systemic shock. The lethal toxin (LeTx) is the major effector of anthrax mortality. Although the mechanism of entry of this toxin into cells is well understood, its actions once inside the cell are not as well understood. LeTx is known to cleave and inactivate MAPKKs. We have recently shown that LeTx represses the glucocorticoid receptor (GR) both in vitro and in vivo. This repression is partial and specific, repressing the glucocorticoid, progesterone, and estrogen receptor α, but not the mineralocorticoid or estrogen receptor β. This toxin does not affect GR ligand or DNA binding, and we have suggested that it may function by removing/inactivating one or more of the many cofactors involved in nuclear hormone receptor signaling. Although the precise involvement of this nuclear hormone receptor repression in LeTx toxicity is unknown, examples of blunted HPA axis and glucocorticoid signaling in numerous autoimmune/inflammatory diseases suggest that such repression of critically important receptors could have deleterious effects on health.

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