Gcn2 Mediates Gcn4 Activation in Response to Glucose Stimulation or UV Radiation Not via GCN4 Translation

• Published in: The Journal of biological chemistry Vol. 276; no. 20; pp. 16944 - 16951
• Main Authors: Marbach, Irit, Licht, Ruth, Frohnmeyer, Hanns, Engelberg, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18-05-2001; American Society for Biochemistry and Molecular Biology
• Subjects: Alcohol Oxidoreductases; Amino Acids - metabolism; Aminohydrolases; beta-Galactosidase - genetics; Cyclic AMP - physiology; DNA-Binding Proteins; Enzyme Activation; Eukaryotic Initiation Factor-2 - metabolism; Fungal Proteins - genetics; Fungal Proteins - metabolism; Glucose - pharmacology; Protein Biosynthesis; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases; Pyrophosphatases; ras GTPase-Activating Proteins - physiology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - radiation effects; Saccharomyces cerevisiae Proteins; Transcription Factor AP-1 - metabolism; Transcription Factors - genetics; Transcription, Genetic - drug effects; Transcription, Genetic - physiology; Transcription, Genetic - radiation effects; Ultraviolet Rays
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M100383200

In mammalian cells transcription factors of the AP-1 family are activated by either stress signals such as UV radiation, or mitogenic signals such as growth factors. Here we show that a similar situation exists in the yeast Saccharomyces cerevisiae. The AP-1 transcriptional activator Gcn4, known to be activated by stress signals such as UV radiation and amino acids starvation, is also induced by growth stimulation such as glucose. We show that glucose-dependent Gcn4 activation is mediated through the Ras/cAMP pathway. This pathway is also responsible for UV-dependent Gcn4 activation but is not involved in Gcn4 activation by amino acid starvation. Thus, the unusual phenomenon of activation of mitogenic pathways and AP-1 factors by contradictory stimuli through Ras is conserved from yeast to mammals. We also show that activation of Gcn4 by glucose and UV requires Gcn2 activity. However, in contrast to its role in amino acid starvation, Gcn2 does not increase eIF2α phosphorylation or translation of GCN4mRNA in response to glucose or UV. These findings suggest a novel mechanism of action for Gcn2. The finding that Gcn4 is activated in response to glucose via the Ras/cAMP pathway suggests that this cascade coordinates glucose metabolism with amino acids and purine biosynthesis and thereby ensures availability of both energy and essential building blocks for continuation of the cell cycle.