Two 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 identified two homologs for the murine ECA39 in the yeast Saccharomyces cerevisiae, ECA39 and ECA40, as well as two human homologs. These genes show a significant homology to prokaryotic branched-chain amino acid aminotransferase (BCAT) (EC). To understand the function of eukaryotic ECA39 and ECA40, we deleted either gene from the yeast genome. Activity of branched-chain amino acid aminotransferase was measured in the wild-type and mutants with either leucine, isoleucine, or valine as substrates. The results demonstrate that in S. cerevisiae ECA39 and ECA40 code for mitochondrial and cytosolic branched-chain amino acid aminotransferases, respectively. ECA39 is highly expressed during log phase and is down-regulated 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, we do not observe a growth phenotype in eca40Delta cells. We suggest that BCAT is a target for c-Myc activity and discuss the evolutionary conservation of prokaryotic and eukaryotic BCATs and their possible involvement in regulation of cell proliferation.
Eden
A
A
Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem 91904, Israel.
Simchen
G
G
Benvenisty
N
N
D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000201:enzymology; D005656:Fungal Proteins; D015870:Gene Expression; D005800:Genes, Fungal; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010802:Phylogeny; D011506:Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000637:Transaminases / Q000235:genetics*
D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C490590:BCAT1 protein, human; C094227:Bcat1 protein, mouse; D000637:Transaminases; C101168:BAT1 protein, S cerevisiae; C101127:BAT2 protein, S cerevisiae; C019798:branched-chain-amino-acid transaminase