Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates

Abstract

Rst1 and Rst2 repress the mating and filamentous growth responses of S. cerevisiae by directly inhibiting Ste12. Activation of Fus3 or Kss1 may cause phosphorylation-dependent release of Ste12 from Rst1/Rst2 and thereby activate Ste12-dependent transcription.

A walk-through of the yeast mating pheromone response pathway

“…In strains lacking Dig1 and Dig2, pheromone-induced genes are constitutively upregulated [10,122,135]. Dig1 and Dig2 display some sequence similarity to each other over a limited region, but appear to repress Ste12 by different mechanisms.…”

“…The Dig1 and Dig2 proteins bind to and repress Ste12 [29,135]. In strains lacking Dig1 and Dig2, pheromone-induced genes are constitutively upregulated [10,122,135].…”

“…Fus3 and/or Kss1 must be catalytically active in order for pheromone-induced changes in gene expression to occur [53]. Furthermore, Ste12 [17,65], as well as Dig1 and Dig2 [29,135], are substrates of Fus3 and Kss1. Finally, Dig1 and Dig2 appear to bind Ste12 less tightly following pheromone stimulation [29,135].…”

“…Furthermore, Ste12 [17,65], as well as Dig1 and Dig2 [29,135], are substrates of Fus3 and Kss1. Finally, Dig1 and Dig2 appear to bind Ste12 less tightly following pheromone stimulation [29,135]. These data collectively suggest that MAPK-dependent phosphorylation of Ste12 and/or Dig1/2 alters the ability of Dig1/2 to bind to and repress Ste12.…”

Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets

“…Cofactors may also influence TF-dependent recruitment of the transcription machinery to the transcription start site; for example, multiprotein bridging factor 1 (Mbf1p) enhances Gcn4p-dependent transcriptional activation by simultaneously binding the DNA-binding domain of general control nonderepressible 4 (Gcn4p) and a subunit of RNA polymerase II complex (24), or a cofactor may prevent a TF from binding to the promoters of its targets. In nutrient-rich conditions in the absence of mating pheromone, the activator of the mating response, Ste12p, is bound by a downregulator of invasive growth protein (Dig2p), which inhibits binding of Ste12p to the promoters of its target genes (25,26). In the presence of pheromone, Dig2p is phosphorylated and…”