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.
© 1994 American Society for Microbiology. Received 10 January 1994/Returned for modification 23 February 1994/Accepted 7 April 1994. We thank Michael Wigler, Kunihiro Matsumoto, and Clyde Denis for yeast strains. D.E. was supported by a fellowship from the Human Frontier Science Program Organization and is now supported by the Israel Cancer Research Fund. This study was supported by NIH grant GM 47381 (to C.S.P.) and by the Beckman Institute at the California Institute of Technology.
Published - 4929.full.pdf