tailieunhanh - Báo cáo khoa học: Regulation of phospholipid biosynthesis by phosphatidylinositol transfer protein Sec14p and its homologues

Transcription of yeast phospholipid biosynthesis structural genes, which contain an inositol-sensitive upstream activa-ting sequence in their promoters, responds to the availability of the soluble precursors inositol and choline and to changes in phospholipid metabolism. The INO1gene is deregulated (derepressedwhen inositol ispresent)under the conditionsof increased phosphatidylcholine (PtdCho) turnover, as occurs in the sec14Dcki1Dstrain (SEC14encodes the major yeast phosphatidylinositol transfer protein;CKI1encodes choline kinase of the cytidine diphosphate choline pathway of PtdCho biosynthesis). . | Eur. J. Biochem. 271 4401-4408 2004 FEBS 2004 doi Regulation of phospholipid biosynthesis by phosphatidylinositol transfer protein Sec14p and its homologues A critical role for phosphatidic acid Roman Holic Milos Zagorsek and Peter Griac Institute of Animal Biochemistry and Genetics Slovak Academy of Sciences Slovakia Transcription of yeast phospholipid biosynthesis structural genes which contain an inositol-sensitive upstream activating sequence in their promoters responds to the availability of the soluble precursors inositol and choline and to changes in phospholipid metabolism. The INO1 gene is deregulated derepressed when inositol is present under the conditions of increased phosphatidylcholine PtdCho turnover as occurs in the sec14D D strain SEC14 encodes the major yeast phosphatidylinositol transfer protein CKI1 encodes choline kinase of the cytidine diphosphate choline pathway of PtdCho biosynthesis . Five proteins Sfhp share sequence homology with phosphatidylinositol transfer protein Sec14p. Two Sfh2p and Sfh4p when overexpressed largely complement the otherwise essential Sec14p requirement concerning growth and secretion. In this study we analysed the ability of Sec14 homologues to correct the defect in regulation of phospholipid biosynthesis resulting from defective or missing Sec14p. We also analysed how PtdCho turnover relates to the transcriptional regulation of phospholipid biosynthesis. The results show that a none of the Sec14 homologues was able to substitute for Sec14p in its regulatory aspects of phospholipid biosynthesis b removal of phospholipase D activity corrected the aberrant INO1 gene regulation in yeast strains with otherwise high PtdCho turnover and c increased steady-state phosphatidic acid levels correlated with derepressed levels of the INO1 gene. Overall the results support the model in which high phos-phatidic acid levels lead to derepression of the genes of phospholipid biosynthesis Henry .

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