The UV response involving the Ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals.
UV irradiation of mammalian cells activates AP-1 through a Ras-dependent pathway, independently of DNA damage. We show that the yeast S. cerevisiae has a remarkably similar UV response involving the AP-1 factor Gcn4, which is distinct from the DNA damage response. Transcriptional activation of HIS3 and HIS4 by Gcn4 is triggered by UV irradiation in a Ras-dependent fashion. Moreover, resistance of yeast to UV irradiation is correlated with the level of Ras activity and Gcn4 function. Like mammalian cells in which activated Ras leads to increased c-Jun synthesis and phosphorylation, the effects in yeast involve increased translation of GCN4 mRNA and a posttranslational event. However, this effect on GCN4 translation is different from the response to amino acid or purine starvation. Therefore, a UV signaling pathway involving Ras and AP-1 is an ancient and universal mechanism involved in protection against damage to cellular components other than DNA.
Engelberg
D
D
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
Klein
C
C
Martinetto
H
H
Struhl
K
K
Karin
M
M
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005800:Genes, Fungal / Q000235:genetics; D011905:Genes, ras; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D000640:Amitrole