Regulation des TEA/ATTS-Transkriptionsfaktors Tec1 durch die Pheromon-induzierte MAPK-Kaskade und den TOR-Signalweg in Saccharomyces cerevisiae

Die Hefe Saccharomyces cerevisiae ist ein dimorpher Pilz, der abhängig von den Umweltbedingungen verschiedene Wachstumsformen annehmen kann. So ermöglicht ein gutes Nährstoffangebot haploiden Hefezellen die sexuelle Konjugation mit Partnerzellen zur Ausbildung des diploiden Zellstadiums. Bestimmte N...

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Bibliographic Details
Main Author: Brückner, Stefan
Contributors: Mösch, Hans-Ulrich (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2007
Online Access:PDF Full Text
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The yeast Saccharomyces cerevisiae is a dimorphic fungus, which is able to differentiate its growth form depending on the environmental conditions. Under good nutrient conditions, haploid yeast cells can undergo sexual conjugation with a partner cell to form a diploid cell. In contrast, certain conditions of nutrient limitation inhibit conjugation and stimulate an adhesive growth form, which allows cells of the same mating type to form biofilms and to adhere to surfaces. The execution of these different developmental programs is under control of a conserved MAPK module, whose central part consists of the MAPK Fus3 and Kss1 and the transcription factors Ste12 and Tec1. Finally, severe nutrient starvation conditions induce entry into stationary phase, which is under control of the complex TOR signaling network. The focus of this work is on the regulation of the transcription factor Tec1, which is the only representative of the conserved family of eukaryotic TEA/ATTS regulators in yeast. In the first part, this work attends to the question how Tec1 is regulated by the two MAPK Fus3 and Kss1 and how this regulation affects conjugation and biofilm formation. It could be shown that during conjugation Tec1, which is a positive regulator of G1-specific cyclin genes is destabilized and degraded upon Fus3-dependent phosphorylation. Downregulation of Tec1 is prerequisite for efficient cell cycle arrest required for fusion of the sexual partner cells. The MAPK Kss1 also regulates Tec1, however not on the protein level, but on the level of TEC1 gene expression via the transcription factor Ste12. This mechanism is not critical for conjugation, but for adhesive growth and biofilm formation because Tec1 is required for expression of FLO11, a gene encoding for a cell curface flocculine required for cellular adhesion. These results demonstrate that two related MAPK control different developmental programs through differential regulation of a single transcription factor. The second part of this work attends to the question of how Tec1 is regulated by nutrient conditions that lead to entry into stationary phase. It could be shown that Tec1 is also destabilized and degraded in response to severe nitrogen or amino acid starvation. This regulation of the transcription factor does not depend on the MAPK Fus3 and Kss1, but requires components of the TOR signaling pathway, the TOR complex 1, the PP2A-related phosphatase Sit4, the protein kinase Npr1 and the HECT ubiquitin ligase Rsp5. Comparable to the conjugation process, the physiological relevance of nutritionally induced degradation of Tec1 could be the downregulation of G1 cyclin gene expression, which is a prerequisite for entry into stationary phase upon severe nutrient deprivation.