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

Irit Marbach, Ruth Licht, Hanns Frohnmeyer, David Engelberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 GCN4 mRNA 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.

Original languageAmerican English
Pages (from-to)16944-16951
Number of pages8
JournalJournal of Biological Chemistry
Issue number20
StatePublished - 18 May 2001


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