MECHANISM AND CONTROL OF FOLATE POLYGLUTAMATON

卵磷脂聚谷氨酸合成酶（FPGS）催化抗代谢物活化为保留在细胞和线粒体中的代谢物。小鼠组织中FPGS基因的转录仅在作为叶酸代谢专门器官的分化组织中，以及在所有正常和恶性分裂细胞群体中由下游启动子调控的上游启动子的组织特异性激活。这两个启动子的相互调节将被研究，以及从上游启动子转录的FPGS异构体的功能。FPGS的细胞内运输是由上游或下游启动子的转录来保证的，这种转录方式既产生转运到细胞质的FPGS转录本，也产生转运到线粒体室的第二种形式的FPGS转录本。将研究这种贩运的动态和作用。最后，将确定特定肽在酶机制中的作用。

Activation of antimetabolites to metabolites which are retained in cells and mitochondria is catalyzed by the enzyme folylpolyglutamate synthetase (FPGS). Transcription of the FPGS gene in mouse tissues is regulated by the tissue-specific activation of an upstream promoter only in differentiated tissues which serve as specialized organs of folate metabolism, and in all normal and malignant dividing cell populations from a downstream promoter. The recriprical regulation of these two promoters will be studied as will the function of the isoform of FPGS transcribed from the upstream promoter. The intracellular trafficing of FPGS is gaurenteed by the transcription of either upstream or downstream promoter in a manner which produces both a transcript for FPGS which traffices to the cytosol and a second form which traffices to the mitochondrial compartment. The dynamics and functions of this trafficing will be studied. Finally, the role of specific peptides in the enzyme mechanism will be determined.