The activation is very transient and is rapidly inactivated by Fus3

In addition, Kss1 becomes activated in response to pheromone stimulation, but in this case the activation is very transient and is rapidly inactivated by Fus3 via unknown mechanism. Transcription factors that are under the control of Kss1 are Ste12 and Tec1. Ste12 is unique because it is essential for both the pheromone signaling pathway and the invasive growth pathway. In the pheromone pathway, activation of Fus3 promotes the formation of Ste12-Ste12 homodimer, which binds to promoter regions that contain a DNA sequence named pheromone-response-element and drives gene expression specifically required for mating. In the invasive growth pathway, activation of Kss1 promotes the formation of a Ste12Tec1 heterodimer, which binds to filamentation-response-element and promotes the expression of genes required for invasive growth, such as FLO11, whose gene product is an adhesion molecule. Several Onjisaponin-B studies have been carried out to elucidate the mechanisms that regulate the Forsythin activity of Ste12 and Tec1. It has been shown that two transcriptional repressors, i.e., Dig1/Rst1 and Dig2/Rst2, play important roles in repressing the transcription activity of Ste12 and Tec1. Some early reports suggest that phosphorylation of these two repressors by activated MAP kinases such as Kss1 somehow leads to de-repression of Ste12 and Tec1, although mutating all six candidate MAP kinase phosphorylation sites on Dig1 did not appear to significantly alter the transcriptional activity of Tec1. Notably, cells that lack both repressors are still capable of augumenting transcriptional responses from Ste12, indicating the existence of additional mechanism that account for regulation of their activity besides direct repression by Dig1/Rst1 and Dig2/Rst2. In an earlier effort to elucidate the mechanisms by which Tec1 is regulated, we demonstrated that it is modified by small ubiquitin-like modifer. Here we describe the function and regulation of this sumoylation event. We provide evidence that activation of the upstream kinase Kss1 leads to a suppression of Tec1 sumoylation.

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