MOT(3) A ZN FINGER TRANSCRIPTION FACTOR THAT MODULATES GENE-EXPRESSION AND ATTENUATES MATING PHEROMONE SIGNALING IN SACCHAROMYCES-CEREVISIAE

In the yeast Saccharomyces cerevisiae, mating pheromone response is in itiated by activation of a G protein- and mitogen-activated protein (M AP) kinase-dependent signaling pathway and attenuated by several mecha nisms that promote adaptation or desensitization. To identify genes wh ose products negatively regulate pheromone signaling, we screened for mutations that suppress the hyperadaptive phenotype of wild-type cells overexpressing signaling-defective G protein beta subunits. This iden tified recessive mutations in MOT3 which encodes a nuclear protein wit h two Cys(2)-His(2) Zn fingers. MOT3 was found to be a dosage-dependen t inhibitor of pheromone response and pheromone-induced gene expressio n and to require an intact signaling pathway to exert its effects. Sev eral results suggested that Mot3 attenuates expression of pheromone-re sponsive genes by mechanisms distinct from those used by the negative transcriptional regulators Cdc36, Cdc39, and Mot2. First, a Mot3-lexA fusion functions as a transcriptional activator. Second, Mot3 is a dos e-dependent activator of several genes unrelated to pheromone response , including CYC1, SUC2, and LEU2. Third, insertion of consensus Mot3 b inding sites (C/A/T)AGG(T/C)A activates a promoter in a MOT3-dependent manner. These findings, and the fact that consensus binding sites are found in the 5' flanking regions of many yeast genes, suggest that Mo t3 is a globally acting transcriptional regulator. We hypothesize that Mob regulates expression of factors that attenuate signaling by the p heromone response pathway.