The AMPK, Snf1, Negatively Regulates the Hog1 MAPK Pathway in ER Stress Response


All organisms are always exposed to several environmental stresses, including ultraviolet, heat, and chemical compounds. Therefore, every cell possesses defense mechanisms to maintain their survival under stressed conditions. Numerous studies have shown that a family of protein kinases plays a principal role in adaptive response to environmental stresses and perturbation of their regulation is implicated in a variety of human pathologies, such as cancer and neurodegenerative diseases. Elucidation of molecular mechanisms controlling their activities is still important not only for understanding how the organism acquires stress tolerance, but also for development of therapies for various diseases. In Saccharomyces cerevisiae, the Hog1 stress-responsive MAP kinase is activated by ER stress and coordinates a pleiotropic response to ER stress. However, the mechanisms for regulating Hog1 activity during ER stress response remain poorly understood. In this paper, we demonstrate that a Saccharomyces cerevisiae ortholog of mammalian AMP–activated protein kinase (AMPK), Snf1, negatively regulates Hog1 in ER stress response. ER stress induces expression of Ssk1, a specific activator of the Hog1 MAPK cascade. Snf1 lowers the expression level of Ssk1, thereby downregulating the signaling from upstream components to the Hog1 MAPK cascade. The activity of Snf1 is also enhanced by ER stress. Thus, our data suggest that Snf1 plays an important role in regulation of ER stress response signal mediated by Hog1.


Vyšlo v časopise: The AMPK, Snf1, Negatively Regulates the Hog1 MAPK Pathway in ER Stress Response. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005491
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005491

Souhrn

All organisms are always exposed to several environmental stresses, including ultraviolet, heat, and chemical compounds. Therefore, every cell possesses defense mechanisms to maintain their survival under stressed conditions. Numerous studies have shown that a family of protein kinases plays a principal role in adaptive response to environmental stresses and perturbation of their regulation is implicated in a variety of human pathologies, such as cancer and neurodegenerative diseases. Elucidation of molecular mechanisms controlling their activities is still important not only for understanding how the organism acquires stress tolerance, but also for development of therapies for various diseases. In Saccharomyces cerevisiae, the Hog1 stress-responsive MAP kinase is activated by ER stress and coordinates a pleiotropic response to ER stress. However, the mechanisms for regulating Hog1 activity during ER stress response remain poorly understood. In this paper, we demonstrate that a Saccharomyces cerevisiae ortholog of mammalian AMP–activated protein kinase (AMPK), Snf1, negatively regulates Hog1 in ER stress response. ER stress induces expression of Ssk1, a specific activator of the Hog1 MAPK cascade. Snf1 lowers the expression level of Ssk1, thereby downregulating the signaling from upstream components to the Hog1 MAPK cascade. The activity of Snf1 is also enhanced by ER stress. Thus, our data suggest that Snf1 plays an important role in regulation of ER stress response signal mediated by Hog1.


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