YAP, A NOVEL FAMILY OF 8 BZIP PROTEINS IN SACCHAROMYCES-CEREVISIAE WITH DISTINCT BIOLOGICAL FUNCTIONS

Saccharomyces cerevisiae contains eight members of a novel and fungus- specific family of bZIP proteins that is defined by four atypical resi dues on the DNA-binding surface. Two of these proteins, Yap1 and Yap2, are transcriptional activators involved in pleiotropic drug resistanc e. Although initially described as AP-1 factors, at least four Yap pro teins bind most efficiently to TTACTAA, a sequence that differs at pos ition +/-2 from the optimal AP-1 site (TGACTCA); further, a Yap-like d erivative of the AP-1 factor Gcn4 (A239Q S242F) binds efficiently to t he Yap recognition sequence. Molecular modeling suggests that the Yap- specific residues make novel contacts and cause physical constraints a t the +/-2 position that may account for the distinct DNA-binding spec ificities of Yap and AP-1 proteins. To various extents, Yap1, Yap2, Ya p3, and Yap5 activate transcription from a promoter containing a Yap r ecognition site. Yap-dependent transcription is abolished in strains c ontaining high levels of protein kinase A; in contrast, Gcn4 transcrip tional activity is stimulated by protein kinase A. Interestingly, Yap1 transcriptional activity is stimulated by hydrogen peroxide, whereas Yap2 activity is stimulated by aminotriazole and cadmium. In addition, unlike other yap mutations tested, yap4 (cin5) mutations affect chrom osome stability, and they suppress the cold-sensitive phenotype of yap 1 mutant strains. Thus, members of the Yap family carry out overlappin g but distinct biological functions.