Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast.
The yeast MAPK pathways required for mating versus filamentous growth share multiple components yet specify distinct programs. The mating-specific MAPK, Fus3, prevents crosstalk between the two pathways by unknown mechanisms. Here we show that pheromone signaling induces Fus3-dependent degradation of Tec1, the transcription factor specific to the filamentation pathway. Degradation requires Fus3 kinase activity and a MAPK phosphorylation site in Tec1 at threonine 273. Fus3 associates with Tec1 in unstimulated cells, and active Fus3 phosphorylates Tec1 on T273 in vitro. Destruction of Tec1 requires the F box protein Dia2 (Digs-into-agar-2), and Cdc53, the Cullin of SCF (Skp1-Cdc53-F box) ubiquitin ligases. Notably, mutation of the phosphoacceptor site in Tec1, deletion of FUS3, or deletion of DIA2 results in a loss of signaling specificity such that pheromone pathway signaling erroneously activates filamentation pathway gene expression and invasive growth. Signal-induced destruction of a transcription factor for a competing pathway provides a mechanism for signaling specificity.
Bao
Marie Z
MZ
Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, CA 94143, USA.
Schwartz
Monica A
MA
Cantin
Greg T
GT
Yates
John R
JR
Madhani
Hiten D
HD
D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010675:Pheromones / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D044843:SKP Cullin F-Box Protein Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism
C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; C495983:Dia2 protein, S cerevisiae; D044783:F-Box Proteins; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; C069926:TEC1 protein, S cerevisiae; D014157:Transcription Factors; D025801:Ubiquitin; D013912:Threonine; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases; C075580:FUS3 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases