HAP4, the glucose-repressed regulated subunit of the HAP transcriptional complex involved in the fermentation-respiration shift, has a functional homologue in the respiratory yeast Kluyveromyces lactis

In Saccharomyces cerevisiae, the heteromeric HAP transcription factor is ne cessary for optimal growth on respiratory carbon sources. one of its compon ents, the Hap4p protein, is necessary for transcriptional activation. The s ame protein is also the regulatory part of the complex in response to carbo n sources, as HAP4 is strongly induced during the shift from fermentative t o respiratory metabolism in S. cerevisiae, We report here the characterizat ion of a new gene from the respiratory yeast Kluyveromyces lactis, obtained by heterologous complementation of a Delta hap4 S, cerevisiae mutant strai n. The deduced sequence of the protein (643 amino acids) exhibits two small domains (11 and 16 amino acids respectively) highly homologous to correspo nding domains of ScHap4p, while the overall similarity is rather weak. Addi tional experiments were performed to confirm the functional homology of thi s new gene with ScHAP4, which we named KIHAP4. The importance of the small highly conserved N-terminal sequence was confirmed by in vitro mutagenesis. All the mutations that interfere with the Hap4p-Hap2/3/5 interaction were localized in it. The discovery of the same regulatory protein in two metabo lically distinct yeast species raises the question of its functional signif icance during evolution.