Transcription profiling of Saccharomyces cerevisiae reveals the Cbf1 basic helix-loop-helix transcription factor is required for the response to hydrogen peroxide stress

ABSTRACT: Cbf1 is a basic helix-loop-helix transcription factor which regulates the expression of many genes of the sulphur assimilation pathway in yeast. Gamma-glutamylcysteine synthetase (GSH1), encoding the rate-limiting enzyme in glutathione biosynthesis, is constitutively elevated in cbf1 mutants indicating that Cbf1 normally represses GSH1 expression. We used transcriptional profiling to show that a number of antioxidant and stress genes are similarly repressed by Cbf1, consistent with the high oxidant tolerance of cbf1 mutants. Our data indicate that Cbf1 plays a key role in the regulation of gene expression during oxidative stress conditions induced by exposure to hydrogen peroxide. The Yap1 transcription factor induces GSH1 expression in response to hydrogen peroxide in a mechanism that does not require the Met4 transcription factor to overcome the inhibitory action of Cbf1. We show that hydrogen peroxide does not affect Cbf1 occupancy on the GSH1 promoter, but results in specific modification of Cbf1 by phosphorylation. Our data indicate that casein kinase (CK2) can directly phosphorylate Cbf1 in vitro. Furthermore, CK2 activity is required to phosphorylate Cbf1 and induce GSH1 expression in yeast cells in response to hydrogen peroxide. CK2 mutants are sensitive to hydrogen peroxide consistent with a role for CK2 in regulating the cellular response to oxidative stress. CK2 is a ubiquitous serine/threonine protein kinase and the finding that it is regulated by oxidative stress is particularly interesting, since there is increasing evidence that it is involved in a number of pathological conditions including cancer, neurodegenerative and cardiovascular diseases.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Andy Hayes 

PROVIDER: E-MEXP-2159 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress