Gcn4p, a master regulator of gene expression, is controlled at multiple levels by diverse signals of starvation and stress
All cells undergo rapid transcriptional reprogramming in response to environmental changes by mobilizing transcriptional activators and repressors. Transcriptional activator proteins function by binding to specific DNA sequences and recruiting the transcriptional machinery to the promoters of genes under their control. Various mechanisms have been elucidated for stimulating activator function in response to environmental signals. For example, when cells of the yeast Saccharomyces cerevisiae are shifted to medium with galactose as a carbon source, the activator Gal4p is released from the inhibitory effects of the repressor Gal80p, which binds to the Gal4p activation domain (43). Other yeast transcriptional activators are regulated at the level of nuclear localization. This group includes Pho4p, Gln3p, and Yap1p, whose presence in the nucleus is coupled to the levels of inorganic phosphate, the quality of the nitrogen source, and oxidative stress, respectively (3, 45). The activator Gcn4p is regulated by a unique translational control mechanism that increases the cellular concentration of Gcn4p in amino acid-starved cells, where increased transcription of amino acid biosynthetic genes under its control is essential to maintaining cell growth (36).