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Novel Repression of the Glucocorticoid Receptor by Anthrax Lethal Toxin
Author(s) -
WEBSTER JEANETTE I.,
MOAYERI MAHTAB,
STERNBERG ESTHER M.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1321.003
Subject(s) - glucocorticoid receptor , psychological repression , nuclear receptor , receptor , glucocorticoid , biology , toxin , mineralocorticoid receptor , estrogen receptor , microbiology and biotechnology , endocrinology , genetics , transcription factor , gene , gene expression , cancer , breast cancer
A bstract : 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.