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Identification of Peroxisomal Targeting Signals in Cholesterol Biosynthetic Enzymes

出版	University of California, San Diego, 2000
URL	http://books.google.com.hk/books?id=XLYJldBkKP0C&hl=&source=gbs_api

註釋A number of proteins required for cholesterol biosynthesis have recently been suggested to be peroxisomal. However, the only enzyme for which a specific peroxisomal targeting signal has been identified is isopentenyl diphosphate isomerase (IPPI) (Paton, V.G., Shackelford, J.E. and Krisans, S.K. 1997. J. Biol. Chem. 272:18945-18950). The studies presented here provide further evidence that peroxisomes contain the cholesterol biosynthetic enzymes required for the conversion of acetyl CoA to farnesyl diphosphate. Furthermore, we have identified the peroxisomal targeting signals required by acetoacetyl CoA thiolase, HMG CoA synthase, phosphomevalonate kinase (PMvK), mevalonate diphosphate decarboxylase (MPD) and farnesyl diphosphate synthase (FPPS). PMvK and acetoacetyl CoA thiolase are targeted to peroxisomes through the PTS-1 sequences, SRL and QKL, respectively. In addition PMvK has been localized to chromosome 1 and the vast majority of its genomic sequence has been identified. These studies also identify a new variation of the PTS-2 found in both MPD and HMG CoA synthase. Furthermore, a 20 amino acid region at the amino terminal of FPPS was shown to contain a peroxisomal targeting sequence with the sequence KL (X5) QE being specifically required. In addition, data obtained from enzymatic regulation studies indicates that the mRNA and enzyme activities for PMvK and MPD are coordinately regulated with HMG CoA reductase, mevalonate kinase and IPPI of the cholesterol biosynthetic pathway in response to sterol availability. These data represent the first individual study in which coordinate regulation of the cholesterol biosynthetic pathway has been analyzed.