Disease relevance of FDPS

• Partial cDNAs for the human farnesyl pyrophosphate synthetase were isolated by screening human hepatoma (HepG2) and placental cDNA libraries with the rat liver cDNA for farnesyl pyrophosphate synthetase as a probe [1].
• TNF, PC, and FPS levels were normal during episodes of cyclosporine toxicity and viral infection.(ABSTRACT TRUNCATED AT 400 WORDS)[2]
• On multivariate analysis, better FPS (0-1; odds ratio, 4; P=0.001) and limited peritoneal metastasis (P1 or P2; 2; P=0.01) were independently associated with improved survival [3].
• Oncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase [4].
• Finally, HTLV-1 p13(II) was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins [4].

Psychiatry related information on FDPS

• In the first phase, the FPS was revised from its original seven faces to six, while maintaining its desirable psychometric properties, in order to make it compatible in scoring with other self-rating and observational scales which use a common metric (0-5 or 0-10) [5].
• CONCLUSIONS: FPS holds promise for reducing child behavior problems, the most common and persistent sequelae of TBI [6].
• OBJECTIVE: To describe a family-centered problem-solving intervention (FPS) for pediatric traumatic brain injury (TBI), and to assess the efficacy of the intervention in a randomized clinical trial [6].

High impact information on FDPS

• Plasma TNF levels were significantly and inversely correlated with PC-Ag (p less than 0.001) and FPS (p less than 0.005) levels during rejection, regardless of whether such rejection episodes were steroid responsive or required OKT3 monoclonal antibody therapy [2].
• Addition of A23187 to the human monocytic leukemia cell line THP-1 in the presence of fetal calf serum led to rapid increases in mRNA concentration of up to 40-fold for HMG-CoA synthase and 15-fold for HMG-CoA reductase with little or no change in FPP synthetase mRNA levels [7].
• The nucleotide sequence of the human farnesyl pyrophosphate synthetase cDNA has high identity (86%) to the rat liver cDNA [1].
• Treatment of the human monocytic leukemia cell line THP-1 with phorbol esters led to 2--7-fold increases in mRNA concentrations for the three cholesterogenic enzymes, farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and HMG-CoA synthase within 5 h [1].
• Nine populations (Germans, Turks, Moroccans, Ovambos, Ugandans, Chinese, Japanese, Papuans, and Australian Aborigines) were investigated using six microsatellite systems (HumCD4, Hum F13B, HumFES/FPS, HumTH01, HumVWA, and D21S11), so-called STRs (short tandem repeats) [8].

Biological context of FDPS

• Considerable nucleotide and deduced amino acid sequence homology is observed between hpt807 and previously isolated rat liver cDNAs for farnesyl pyrophosphate synthetase [9].
• FPS gene expression is also under strict developmental control: FPS mRNA was mainly abundant in young organs and decreased as organs matured with the exception of fruits that presented a biphasic accumulation pattern [10].
• Taken together our results suggest that several FPS isoforms are involved in tomato farnesyl pyrophosphate metabolism and that FPS genes are mostly expressed in relation to cell division and enlargement [10].
• A system of four short tandem repeat loci (HUMVWF31A, HUMTH01, HUMF13A1, and HUMFES/FPS) has been tested in co-amplification with forensic (post-mortem and post-coital) DNA samples [11].
• Six microsatellite - or short tandem repeat (STR) - systems with uniform repetitive sequences (HumTH01, HumCD4, HumFES/FPS, HumF13B, HumTPO, HumLPL) and three compound repeat systems (HumVWA, HumFIBRA, D21S11) were used, including data from the literature, to determine genetic distances among eight populations worldwide [12].

Anatomical context of FDPS

• FPS is overexpressed in the corpora allata, the endocrine gland that produces the juvenile hormones [13].
• Using an RNase protection assay, a protected fragment corresponding to the region encoding the FPS catalytic site was found in brain, ovary, fat body and corpora allata samples, but not in muscle [13].
• The timing of FPS in either cranial base of mandible was not closely related to the onset of ossification in the ulnar sesamoid, the age at peak height velocity, or age at menarche [14].

Associations of FDPS with chemical compounds

• Comparison with rat cDNAs suggests that hpt807 is about 20 bp short of encoding the initiator methionine of farnesyl pyrophosphate synthetase [9].
• Lovastatin increases mRNA levels for farnesyl pyrophosphate synthetase 2.5-fold while mevalonic acid, low-density lipoprotein, and 25-hydroxycholesterol decrease mRNA levels to 40-50% of control values [9].
• Cholesterol biosynthesis is under feedback regulation, and the cellular and circulating cholesterol levels are tightly regulated at several points, such as the rate limiting enzyme 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase and farnesyl pyrophosphate synthetase and at the low density lipoprotein (LDL) receptor [15].
• Calcium ionophore treatment impairs the sterol-mediated suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 3-hydroxy-3-methylglutaryl-coenzyme A synthase, and farnesyl diphosphate synthetase [7].
• Consistent with farnesyl pyrophosphate requirement in sterol biosynthesis, FPS genes are ubiquitously expressed in tomato plants [10].

Other interactions of FDPS

• In support of the concept of RhoB as a negative regulator of Ras signaling pathways, the most strongly downregulated gene scored was farnesyl pyrophosphate synthetase, the enzyme that produces the substrate used by FT to farnesylate Ras proteins [16].

Analytical, diagnostic and therapeutic context of FDPS

• In this latter case in situ hybridization studies have shown that FPS mRNA is similarly abundant in all tissues of young fruit [10].
• Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS [4].
• Using a computer-animated version of the FPS developed by Champion and colleagues (Sydney Animated Facial Expressions Scale), psychophysical methods were applied to identify four faces representing equal intervals between the scale values representing least pain and most pain [5].
• In this study three STR loci, HUMFES/FPS, HUMTH01, and HUMVWA31A, were selected to estimate their usefulness when applied to recent and ancient spongy bone DNA typing [17].
• Prenyltransferase (farnesyl pyrophosphate synthetase) was purified from avian liver and characterized by Sephadex and sodium dodecyl sulfate gel chromatography, peptide mapping, and end-group analysis [18].

References