MOLECULAR-CLONING OF MURINE FOLYLPOLY-GAMMA-GLUTAMATE SYNTHETASE

Folylpoly-gamma-glutamate synthetase (FPGS) is essential for mammalian cell survival and is a major determinant of cytotoxicity and selectiv ity for folate antimetabolites. Here we describe the cloning of a cDNA encoding murine FPGS isolated from L1210 leukemia cells. The amino ac id sequence of murine FPGS is 82% identical to human FPGS [1] with ide ntical discrete regions of up to 41 residues. Murine FPGS contains two AUG initiation codons, shown to be responsible for mitochondrial and cytosolic forms of the enzyme in human cells [2]. Previous studies ind icated species, tissue, and tumor specific differences in mammalian FP GS. The availability of murine FPGS expands the knowledge and understa nding of the spectrum of these variations.