出版社：American Society for Biochemistry and Molecular Biology
摘要：Pantothenate kinase (PanK) is thought to catalyze the first rate-limiting step in CoA biosynthesis. The full-length cDNA encoding the human PanK1α protein was isolated, and the complete human PANK1 gene structure was determined. Bezafibrate (BF), a hypolipidemic drug and a peroxisome proliferator activator receptor-α (PPARα) agonist, specifically increased hPANK1 α mRNA expression in human hepatoblastoma (HepG2) cells as a function of time and dose of the drug, compared with hPANK1 β, hPANK2 , and hPANK3 , which did not significantly increase. Four putative PPARα response elements were identified in the PANKI α promoter, and BF stimulated hPANK1 α promoter activity but did not alter the mRNA half-life. Increased hPANK1 α mRNA resulted in higher hPanK1 protein, localized in the cytoplasm, and elevated PanK enzyme activity. The enhanced hPANK1 α gene expression translated into increased activity of the CoA biosynthetic pathway and established a higher steady-state CoA level in HepG2 cells. These data are consistent with a key role for PanK1α in the control of cellular CoA content and point to the PPARα transcription factor as a major factor governing hepatic CoA levels by specific modulation of PANK1 α gene expression.
