Signal transduction and transcription in yeast

In signal transduction research, aims have shifted towards gaining a dynamic understanding of such processes. Current questions also concern how multiple signal pathways are integrated to elicit defined responses, how signal/response specificity is maintained when the same factors transmit multiple signals, and how cross talk between different signal systems is either established or avoided.
Our lab has tried to make progress towards such questions by studying the high osmolarity glycerol response in yeast. Upon exposure to osmotically imbalanced environments, yeast cells transiently activate a specific MAP kinase cascade. The transcriptional response coordinated by this MAP kinase, Hog1, has been well characterized. Apart from transcription factors Hog1 also becomes associated with stress induced promoters suggesting that it acts directly on the general transcription machinery. Hog1 is activated via two sensors linked to two separate signaling branches. One of the branches requires the function of signaling factors that are also active in mating and during starvation induced filamentous growth. Signal specificity seems to be maintained through Hog1 dependent feedback control and a scaffolding function of Pbs2, the activator of Hog1. Aims are to find Hog1 targets within this feedback system and to investigate how Pbs2 complexes are formed and disassembled during signaling.

A defined set of genes is induced by a wide variety of stress situations via the zinc finger protein Msn2. Since this response is highly influenced by the nutrient supply, Msn2 can be viewed as integrator of growth and stress signals. Indeed, the principal growth regulator, protein kinase A inhibits directly the nuclear accumulation and DNA binding of Msn2. Since stresses have the opposite effect without changing PKA activity, Msn2 dephosphorylation has recently emerged as overarching theme in stress signal transduction.
Regulated expression of genes that contribute to stage specific functions are a key feature of eukaryotic cell cycles. In budding yeast, one set of genes is induced during the G2/M phase. Expression depends on the activity of the mitotic kinase Cdk1/Clb2. Promoter elements and factors regulating promoter function have been identified. Additionally, it has become clear that the periodic transcription is due to both positive and negative regulatory mechanisms. Apart from defining the interactions of transcriptional regulators, we have tried to determine how Cdk1/Clb2 could modulate their function.

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