Bacillus anthracis edema toxin activates nuclear glycogen synthase kinase 3beta

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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
09:25

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells

Published on: August 19, 2016

Jason L Larabee1, Kevin DeGiusti, James L Regens

  • 1Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

Infection and Immunity
|September 4, 2008
PubMed

Insights

Bacillus anthracis edema toxin (ET) activates nuclear GSK-3beta, arresting the cell cycle. This novel mechanism bypasses cellular defenses, highlighting ET

Area of Science:

  • Cellular and Molecular Biology
  • Microbiology
  • Toxicology

Background:

  • Bacillus anthracis edema toxin (ET) disrupts cellular signaling by increasing cyclic AMP.
  • Understanding ET's impact on kinase pathways is crucial for deciphering its cellular effects.

Purpose of the Study:

  • To identify kinase signaling pathways modulated by ET.
  • To elucidate the mechanism of ET-induced cell cycle arrest.

Main Methods:

  • Utilized small-molecule kinase inhibitors to screen for protective pathways.
  • Employed cell fractionation and confocal immunofluorescence microscopy.
  • Investigated the Wnt signaling pathway and beta-catenin regulation.

Main Results:

  • GSK-3beta inhibitors protected cells from ET-induced cell cycle changes.
  • ET specifically activates nuclear GSK-3beta, not cytoplasmic.
  • Nuclear GSK-3beta inactivation of beta-catenin was observed post-intoxication.
  • ET circumvents Wnt-3A-mediated cytoplasmic GSK-3beta inactivation.

Conclusions:

  • ET arrests the cell cycle via activation of nuclear GSK-3beta.
  • This nuclear targeting represents a novel intoxication mechanism, evading cellular counter-regulation.

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