Rat Liver Carbamoyl Phosphate Synthetase Enzyme I Gene 5 'upstream Dna Specific Binding Protein

It is generally realized that neoplastic transfermation is closely related with abnormal cell proliferation. The abnormal cell differentiation may play a more important part in the process of oncogenesis. Carbamyl Phosphate Synthetase I (CPSI) is the first key enzyme of urea cycle. It is a liver specific enzyme, mainly localized in mitochodria. Our previous work has shown that the activity of CPSI was decreased during hepato-carcinogenesis induced by diethylnitrosamine, and the decrease in enzyme activity was substantiated to be attributed to changes in the amount of enzyme protein and the rate of protein biosynthesis. RNA-DNA hybridization revealed a decrease in CPSI mRNA content during hepatocarcinogenesis. The alteration of CPSI gene expression in hepatoma cells was closely correlated to that of chromatin structure. All these results suggested that changes in CPSI expression during hepato-carcinogenesis would be resulted from an aberration in gene regulation at the transcriptional level. The fact that interaction between trans-acting factors and cis-acting elements is of primary importance in studies on the transcriptional control of gene expression prompted us to identify specific DNA-binding protein(s) in the 5' upstream of CPSI gene which would be closely involved in elucidation of the mechanism of gene regulation of CPSI in both normal and malignant hepatocytes.The CPSI genomic clone containint 5' upstream sequence was first prepared by screening from rat liver gene library with a synthetic...