2 YEAST HOMOLOGS OF ECA39, A TARGET FOR C-MYC REGULATION, CODE FOR CYTOSOLIC AND MITOCHONDRIAL BRANCHED-CHAIN AMINO-ACID AMINOTRANSFERASES

ECA39 was isolated as a target gene for c-Myc regulation in mice. We i dentified two homologs for the murine ECA39 in the yeast Saccharomyces cerevisiae, ECA39 and ECA40, as well as two human homologs. These gen es show a significant homology to prokaryotic branched-chain amino aci d aminotransferase (BCAT) (EC 2.6.1.42). To understand the function of eukaryotic ECA39 and ECA40, we deleted either gene hom the yeast geno me. Activity of branched-chain amino acid aminotransferase was measure d in the wild-type and mutants with either leucine, isoleucine, or val ine as substrates. The results demonstrate that in S. cerevisiae ECA39 and ECA40 code for mitochondrial and cytosolic branched-chain amino a cid aminotransferases, respectively. ECA39 is highly expressed during log phase and is downregulated during the stationary phase of growth, while ECA40 shows an inverse pattern of gene expression. In agreement with these results, while we previously showed that deletion of ECA39 affected the cell cycle in proliferating cells, me do not observe a gr owth phenotype in eca40 Delta cells. We suggest that BCAT is a target for c-Myc activity and discuss the evolutionary conservation of prokar yotic and eukaryotic BCATs and their possible involvement in regulatio n of cell proliferation.