The yeast and mammalian Ras pathways control transcription of heat shock genes independently of heat shock transcription factor.
Yeast strains in which the Ras-cyclic AMP (cAMP) pathway is constitutively active are sensitive to heat shock, whereas mutants in which the activity of this pathway is low are hyperresistant to heat shock. To determine the molecular basis for these differences, we examined the transcriptional induction of heat shock genes in various yeast strains. Activation of heat shock genes was attenuated in the strains in which the Ras-cAMP pathway is constitutively active. In contrast, in a strain deficient in cAMP production, several heat shock genes were induced by removal of cAMP from the medium. These results indicate that the Ras-cAMP pathway affects the induction of heat shock genes. In all of the mutants, heat shock transcription factor expression and activity were identical to those in wild-type cells. The response to heat shock in Ha-ras-transformed rat fibroblasts was also studied. While no induction of Hsp68 was observed in Ha-ras-transformed cells, proper regulation of heat shock transcription factor was found. Therefore, in mammals, as in Saccharomyces cerevisiae, the Ras pathway controls the transcription of heat shock genes via a mechanism not involving the heat shock transcription factor.
Engelberg
D
D
Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla 92093-0636.
Zandi
E
E
Parker
C S
CS
Karin
M
M
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D011905:Genes, ras; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D018631:ras Proteins
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins