Reference - Detail
|Author||Umekawa M, Ujihara M, Makishima K, Yamamoto S, Takematsu H, Wakayama M.|
|Title||The signaling pathways underlying starvation-induced upregulation of α-mannosidase Ams1 in Saccharomyces cerevisiae.|
|Journal||Biochim. Biophys. Acta|
BACKGROUND:Cells have evolved the mechanisms to survive nutritional shortages in the environment. In Saccharomyces cerevisiae, α-mannosidase Ams1 is known to play a role in catabolism of N-linked free oligosaccharides in the cytosol. Although, this enzyme is also known to be transported selectively from the cytosol to the vacuoles by autophagy, the physiological significance of this transport has not been clarified.
METHODS:To elucidate the regulatory mechanism of the activity of Ams1, we assessed the enzymatic activity of the cell free extract of the wild-type and various gene disruptants under different nutritional conditions. In addition, the regulation of Ams1 at both transcription and post-translation was examined.
RESULTS:The activity of Ams1 was significantly increased upon the depletion of glucose in the medium. Interestingly, the activity of the enzyme was also stimulated by nitrogen starvation. Our data showed that the activity of Ams1 is regulated by the stress responsive transcriptional factors Msn2/4 through the protein kinase A and the target of rapamycin complex 1 pathways. In addition, Ams1 is post-translationally activated by Pep4-dependent processing in the vacuoles.
CONCLUSION:Yeast cells monitor extracellular nutrients to regulate mannoside catabolism via the cellular signaling pathway.
GENERAL SIGNIFICANCE:This study revealed that intracellular Ams1 activity is exquisitely upregulated in response to nutrient starvation by induced expression as well as by Pep4-dependent enhanced activity in the vacuoles. The signaling molecules responsible for regulation of Ams1 were also clarified.
|MeSH||Aspartic Acid Endopeptidases / physiology Cyclic AMP-Dependent Protein Kinases / physiology Glucose / metabolism Mechanistic Target of Rapamycin Complex 1 Multiprotein Complexes / physiology Nitrogen / metabolism Protein-Serine-Threonine Kinases / physiology Saccharomyces cerevisiae / enzymology* Saccharomyces cerevisiae Proteins / physiology Signal Transduction / physiology* TOR Serine-Threonine Kinases / physiology Up-Regulation alpha-Mannosidase / metabolism*|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY BIOPHYSICS|