Characterization of ECA39, a genetic target for c-myc regulation, in yeast, mice and man

EC439 was identified as a target for c-Myc regulation in transgenic mice. To further characterize this target gene, we have isolated the human, nematode and budding yeast homologs of the mouse gene. ECA39 was shown to be a target for c-myi oncogenesis in man: A Myc binding site appears close to the human ECA39 promoter; Chimeric constructs with human sequences response to over-expression of c-myc; EC/439 is expressed in Burkitt's lymphoma (where c-myc is translocated and activated) but not in non Burkitt's B-cell lymphoma or in Tcell lymphoma. In yeast, where c-myc is absent, the regulator is not c-Myc but the c-Jun/c-Fos homolog - Gcn4: The promoter region of the yeast EC/439 harbors several Gcn4 binding elements, and EC/439 is down regulated in gcn4A cells. Recently, A gene similar to ECA39, named ECA40, was identified in both budding yeast and man. Both EC/439 and EC/440 show a significant homology to prokaryotic branched-chain amino acid aminotransferase (BCAT). Using genetic manipulations in yeast, we have demonstrated that EC/439 and EC/440 code for mitochondrial and cytosolic BCATs, respectively.