Attachment of the prenyl groups farnesyl and geranylgeranyl to specific eukaryotic cell proteins by protein prenyltransferases is required for the functioning of a number of cellular processes including signal transduction. In this study it was found that previously reported inhibitors of mammalian protein farnesyltransferase (PFT) [those that mimic the substrate farnesyl pyrophosphate and thos...

The structures of new protein farnesyltransferase inhibitors, kurasoins A and B, were elucidated by NMR study. Kurasoins A and B are acyloin compounds having in common a 3-hydroxy-1-phenyl-2-butanone moiety, to which p-hydroxyphenyl and 3-indolyl moieties respectively, are connected at C-4. The structures were confirmed by total synthesis.

New studies in Drosophila have identified a novel nuclear envelope protein with a farnesyl moiety, termed Kugelkern/Charleston, that helps regulate the size, shape and position of cellular blastoderm nuclei.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is characterized by dramatic premature aging and accelerated cardiovascular disease. HGPS is almost always caused by a de novo point mutation in the lamin A gene (LMNA) that activates a cryptic splice donor site, producing a truncated mutant protein termed "progerin." WT prelamin A is anchored to the nuclear envelope by...

G protein gamma-subunits are isoprenylated and carboxyl methylated at the C-terminal cysteine residue, and the set of the posttranslational modifications is indispensable for the function of the photoreceptor G protein transducin (Talpha/Tbetagamma). To explore farnesyl-mediated molecular interactions, we investigated molecular targets of a Tbetagamma analogue that was engineered to have a phot...

We previously reported that squalestatin 1-mediated induction of CYP2B expression is attributable to squalene synthase inhibition and accumulation of an endogenous isoprenoid(s) that is capable of activating the constitutive androstane receptor. To determine whether squalestatin 1-mediated CYP2B induction is strictly dependent on the biosynthesis of farnesyl pyrophosphate (FPP), the substrate f...

A trans-farnesyl pyrophosphate-squalene synthetase has been isolated in a soluble form from yeast extracts and purified 45fold. The molecular weight of the enzyme estimated from sucrose density gradient centrifugation and gel filtration chromatography is 426,000. Solubilization of the squalene synthetase is achieved with deoxycholate. Treatment with the detergent markedly lowers squalene synthe...

It has been proposed that isoprenoid biosynthesis in several gram-positive cocci depends on the mevalonate pathway for conversion of acetyl coenzyme A to isopentenyl diphosphate. Mevalonate kinase catalyzes a key reaction in this pathway. In this study the enzyme from Staphylococcus aureus was expressed in Escherichia coli, isolated in a highly purified form, and characterized. The overall amin...

Cancer cells are more addictive to MTH1 than normal cells because of their dysfunctional redox regulations. MTH1 plays an important role to maintain tumor cell survival, while it is not indispensable for the growth of normal cells. Farnesyl phenols having a coumaroyl substitution are rather uncommon in nature. Eight farnesyl phenolic compounds with such substituent moiety (1-8), including six n...

Chs4p (Cal2/Csd4/Skt5) was identified as a protein factor physically interacting with Chs3p, the catalytic subunit of chitin synthase III (CSIII), and is indispensable for its enzymatic activity in vivo. Chs4p contains a putative farnesyl attachment site at the C-terminal end (CVIM motif) conserved in Chs4p of Saccharomyces cerevisiae and other fungi. Several previous reports questioned the rol...