Analyzing the postulated inhibitory effect of Manumycin A on farnesyltransferase.

Manumycin A is postulated to be a specific inhibitor against the farnesyltransferase (FTase) since this effect has been shown in 1993 for yeast FTase. Since then, plenty of studies investigated Manumycin A in human cells as well as in model organisms like Some studies pointed to additional targets and pathways involved in Manumycin A effects like apoptosis. Therefore, these studies created doubt whether the main mechanism of action of Manumycin A is FTase inhibition.

Impact of a conserved N-terminal proline-rich region of the α-subunit of CAAX-prenyltransferases on their enzyme properties.

Background: The CAAX-prenyltransferases farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) are heterodimers with a common α- (FTα) and unique β-subunits. Recently, α-subunits of species (e.g.

Characterization of the promoter of the human farnesyltransferase beta subunit and the impact of the transcription factor OCT-1 on its expression.

Farnesyltransferase (FTase) enables about 100 proteins to interact with cellular membranes by catalyzing the posttranslational addition of a farnesyl group. Farnesylated proteins provide important functions and inhibitors against the β-subunit of the heterodimer of FTase are intensively studied in clinical and preclinical trials. However, very little is known about the transcriptional regulation of the β-subunit.

Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase.

Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickness, leishmaniosis, and hepatitis D virus infection. Little is known about protein prenylation mechanisms in human pathogens.

Salt Stress Response of Sulfolobus acidocaldarius Involves Complex Trehalose Metabolism Utilizing a Novel Trehalose-6-Phosphate Synthase (TPS)/Trehalose-6-Phosphate Phosphatase (TPP) Pathway.

The crenarchaeon has been described to synthesize trehalose via the maltooligosyltrehalose synthase (TreY) and maltooligosyltrehalose trehalohydrolase (TreZ) pathway, and the trehalose glycosyltransferring synthase (TreT) pathway has been predicted. Deletion mutant analysis of strains with single and double deletions of Δ and Δ in revealed that in addition to these two pathways, a third, novel trehalose biosynthesis pathway is operative : the trehalose-6-phosphate (T6P) synthase/T6P phosphatase (TPS/TPP) pathway. In contrast to known TPS proteins, which belong to the GT20 family, the TPS belongs to the GT4 family, establishing a new function within this group of enzymes.

SNPs Within the MTOR Gene Are Associated With an Increased Risk of Developing De Novo Diabetes Mellitus Following the Administration of Everolimus in Liver Transplant Recipients.

Background: The impact of immunosuppressive drugs in patients following liver transplantation (LT) is very individual. Despite the multiple beneficial effects of the mammalian target of rapamycin (mTOR) inhibitor everolimus (EVR) in LT recipients, some patients do not benefit from EVR administration. We investigated whether the presence of common single-nucleotide polymorphisms (SNPs) in the mTOR gene are predictive for adverse events following the introduction of EVR after LT.

Exploring the putative self-binding property of the human farnesyltransferase alpha-subunit.

Farnesylation is an important post-translational protein modification in eukaryotes. Farnesylation is performed by protein farnesyltransferase, a heterodimer composed of an α- (FTα) and a β-subunit. Recently, homodimerization of truncated rat and yeast FTα has been detected, suggesting a new role for FTα homodimers in signal transduction.

In vitro performance of zirconia and titanium implant/abutment systems for anterior application.

Objectives: To investigate the type of failure and fracture resistance behaviour of different zirconia and titanium implant/abutment systems for anterior application.

Methods: Eight groups of implant-abutment combinations (n=8/system) were restored with identical full-contour zirconia crowns. The systems represented one-piece and multi-piece zirconia (Z) or titanium (T) implants/abutments with different types of connection (screwed=S, bonded=B).

The first prokaryotic trehalose synthase complex identified in the hyperthermophilic crenarchaeon Thermoproteus tenax.

The role of the disaccharide trehalose, its biosynthesis pathways and their regulation in Archaea are still ambiguous. In Thermoproteus tenax a fused trehalose-6-phosphate synthase/phosphatase (TPSP), consisting of an N-terminal trehalose-6-phosphate synthase (TPS) and a C-terminal trehalose-6-phosphate phosphatase (TPP) domain, was identified. The tpsp gene is organized in an operon with a putative glycosyltransferase (GT) and a putative mechanosensitive channel (MSC).

Characterization of the CRISPR/Cas subtype I-A system of the hyperthermophilic crenarchaeon Thermoproteus tenax.

CRISPR (clustered regularly interspaced short palindromic repeats) elements and cas (CRISPR-associated) genes are widespread in Bacteria and Archaea. The CRISPR/Cas system operates as a defense mechanism against mobile genetic elements (i.e.