Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor.
In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP-dependent protein kinase (cAPK). Genetic analysis suggests that Msn2-NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2-NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full-length Msn2. The Msn2-NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose-sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short-term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5-dependent nuclear export and/or retention mechanism.
Görner
Wolfram
W
Vienna Biocenter, Institut für Biochemie und Molekulare Zellbiologie der Universität Wien and Ludwig Boltzmann-Forschungsstelle für Biochemie, Dr Bohrgasse 9, A-1030 Wien, Austria.
Durchschlag
Erich
E
Wolf
Julia
J
Brown
Elizabeth L
EL
Ammerer
Gustav
G
Ruis
Helmut
H
Schüller
Christoph
C
D001483:Base Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005285:Fermentation; D005947:Glucose / Q000378:metabolism*; D008954:Models, Biological; D009584:Nitrogen / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; D019913:Nuclear Localization Signals; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D009584:Nitrogen