engleski

Novel aspects of Gal4 regulation by Srb10 and mitochondrial dysfunction

Regulation of gene expression by metabolic pathways is a common strategy used by the cell to adjust to its changing energy requirements. One of the best-studied examples of such a mechanism is regulation of Galactose-inducible genes by the prototypical acidic activator Gal4. In this report we have analyzed the influence of mitochondrial dysfunction on Gal4 activity and show that respiratory deficient cells increase Gal4-dependent transcription. We show that the DNA-binding and activation domain of Gal4 are sufficient for this effect. Furthermore, the cyclin dependent kinase Srb10 (cdk8) is necessary for mitochondrial signaling to Gal4, but this effect is independent of Gal4 S699 phosphorylation. Mitochondrial dysfunction appears to affect regulation of Gal4 binding to DNA. We suggest that Srb10 dependent phosphorylation of a yet unidentified site, potentially in the Gal4 DNA binding domain, or modification of other transcription factors that cooperate with Gal4 in the process of transcriptional activation underlies the effect of Srb10 on Gal4 transcription in response to mitochondrial dysfunction.

yeast; Gal4; Srb10; mitochondrial dysfunction

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