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Topic: Prenylation

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	Prenylation - Wikipedia, the free encyclopedia
		Prenylation or isoprenylation or lipidation is the addition of hydrophobic molecules to a protein.
		It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing.
		Prenyl groups have been shown to be important for protein-protein binding through specialized prenyl-binding domains.
	en.wikipedia.org /wiki/Prenylation (675 words)

	Prenylation of Proteins
		These "prenyl" groups are made from the chemical species isoprene, a fundamental and ubiquitous chemical building block in plants and animals.
		Prenyl groups seem to play a role in anchoring proteins to cell membranes, among other functions.
		After Glomset, Gelb, and colleagues had demonstrated the structure of these prenyl groups, researchers elsewhere found that a certain type of protein responsible for cellular switching and growth functions, called the "ras" protein, has a farnesyl group attached to it which is critical to the function of the protein.
	www.washington.edu /research/pathbreakers/1990b.html (1038 words)

	Protein Prenylation
		e have recently shown that protein prenylation occurs in pathogenic microorganisms including Trypanosoma brucei, the causative agent of African sleeping sickness, Trypanosoma cruzi, the causative agent of Chagas' disease, Leishmania spp., the causative agents of leishmaniasis, and Plasmodium falciparum, the causative agent of falciparum malaria.
		In all cases, the prenyl groups are at the C-terminus of the protein, and the
		We are also studying the entire protein prenylation pathway in parasites and have recently cloned the prenyl protein-specific endoprotease and methyltransferase that are involved in the maturation of prenylated proteins.
	faculty.washington.edu /gelb/prenyl.html (590 words)

	Program in Cell and Molecular Biology
		The first is the covalent modification of G proteins by isoprenoid lipids and the role this modification, termed protein prenylation, plays in the membrane targeting and function of G proteins.
		Prenylation plays a crucial role oncogenic transformation by one class of G proteins, the Ras proteins.
		The enzymes that catalyze these modifications have been isolated and cloned and are being used to develop in vitro systems to both define the enzymes structures and molecular mechanisms and elucidate the role of prenylation in G protein function.
	cmb.duke.edu /faculty/casey.html (343 words)

	Preclinical and Clinical Pharmacodynamic Assessment of L-778,123, a Dual Inhibitor of Farnesyl:Protein Transferase and ... (Site not responding. Last check: 2007-08-06)
		inhibit the prenylation of Rap1A, a GGPTase-I substrate, as
		Inhibition of HDJ2 prenylation in mice infused with FTI-1.
		prenylation; this is surprising because the DPI inhibited Rap1A
	mct.aacrjournals.org /cgi/content/full/1/9/747 (7020 words)

	Breast Cancer Research \| Full text \| Prenylation inhibitors stimulate both estrogen receptor alpha transcriptional ...
		Prenylation appears to be essential not only for membrane association, but also for biological activity [16].
		Prenylated proteins have been implicated in both estrogenic actions [17,23], and the prenylated Rho GTPases are now considered important modulators of ER transcriptional activity [24,25].
		Prenylated proteins may then modulate ER signaling through each key step in the various pathways: membrane attachment, translocation to the nucleus, stability, and genomic or nongenomic activities.
	breast-cancer-research.com /content/7/1/R60 (6579 words)

	BioMed Central \| Full text \| Farnesylation or geranylgeranylation? Efficient assays for testing protein prenylation in ...
		Prenylation is a lipid posttranslational modification (PTM) of proteins at cysteine residues in the C-terminal region [1-7].
		Furthermore, there is evidence that inhibitors of prenylation may be useful in the treatment of other diseases such as infestation with protozoa [6,37].
		Given the critical role of the prenyl anchor for biological function (both with respect to the occurrence of prenylation and to the dependence on anchor type), it is of growing interest to analyze the prenylation status of so far uninvestigated proteins and to enlarge the list of proven prenylated proteins.
	www.biomedcentral.com /1471-2091/7/6 (6972 words)

	Tamara A. Kale (Site not responding. Last check: 2007-08-06)
		Other prenylated G proteins acting downstream of Ras are gaining attention as well, such as Rho proteins.(2) Prenylation prevention is a target of therapeutic interest and particular attention has been paid to developing prenyltransferase inhibitors, but another area of therapy could lie in the disruption of prenylated protein-protein interactions.
		Prenylation does encourage membrane attachment of modified proteins, yet evidence suggests another role for isoprenoid addition: proteins may recognize prenylated proteins via the prenyl tail, thereby conferring additional specificity in these interactions.(3) Few details are known concerning specific contacts these tails make with other proteins.
		A radioactive prenylated cysteine mimic with a photoactivatable moiety.
	www.chem.umn.edu /groups/distefano/kale.htm (541 words)

	Molecular Basis for Rab Prenylation -- Alory and Balch 150 (1): 89 -- The Journal of Cell Biology
		and prenylation in vitro, and cell growth and transport in vivo.
		that fail to be prenylated accumulate in the cytosol.
		to prenylate the ER to Golgi complex-specific Rab, Ypt1p.
	www.jcb.org /cgi/content/full/150/1/89 (8415 words)

	Dual Prenylation Is Required for Rab Protein Localization and Function -- Calero et al. 14 (5): 1852 -- Molecular ...
		Prenylation status of Rab proteins is a critical determinant for interactions with Yip1p.
		Martincic, I., Peralta, M.E., and Ngsee, J.K. Isolation and characterization of a dual prenylated Rab and VAMP2 receptor.
		Pereira-Leal, J.B., Hume, A.N., and Seabra, M.C. Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease.
	www.molbiolcell.org /cgi/content/full/14/5/1852 (8167 words)

	Extended presentation (Site not responding. Last check: 2007-08-06)
		This project is directed towards determining the suitability of protein prenyl transferases as targets for chemotherapy of the African trypanosome Trypanosoma brucei.
		brucei, and (4) protein prenylation is a proven target for chemotherapy of cancer, and therefore reagents and inhibitors of the mammalian enzymes have been prepared, providing both a detailed knowledge of the host activities and a potential resource for study of the parasite enzymes.
		brucei prenylation in vivo by study of cell growth, morphology and metabolic labelling of isoprenylated polypeptides and in vitro by assay on prenyl transferase activity directly, and (iii) cloning of the nucleic acids encoding both subunits of the farnesyl and geranylgeranyl transferases.
	www.bio.ic.ac.uk /research/field/prenylation.html (480 words)

	Prenylation inhibitors: a novel class of antiviral agents -- Einav and Glenn 52 (6): 883 -- Journal of Antimicrobial ...
		Prenylation inhibitors: a novel class of antiviral agents -- Einav and Glenn 52 (6): 883 -- Journal of Antimicrobial Chemotherapy
		Prenylation is a site-specific lipid modification of proteins.
		Protein prenylation occurs by the covalent, post-translational addition of either farnesyl or geranylgeranyl to conserved cysteine residues at or near the C-terminus of proteins.
	jac.oxfordjournals.org /cgi/content/full/52/6/883 (2877 words)

	RhoA Prenylation Is Required for Promotion of Cell Growth and Transformation and Cytoskeleton Organization but Not for ...
		Prenylation Status and Subcellular Localization of RhoA Mutants in NIH-3T3 and COS-7 Cell Transfectants-- To evaluate the role of prenyl group and of its nature (C15 farnesyl or C20 geranylgeranyl) in RhoA functions we generated
		Role of Prenylation of RhoA on Cell Growth Properties-- We next assessed the role of the prenylation of RhoA on cell growth.
		Prenylated RhoA was detected in the cytoplasmic compartment in NIH-3T3 cells stably transfected with RhoA, as previously observed
	www.jbc.org /cgi/content/full/275/40/31001 (5529 words)

	v-K-ras leads to preferential farnesylation of p21ras in FRTL-5 cells: Multiple interference with the isoprenoid ...
		Alterations in prenylation pattern are a specific marker of active K-ras.
		The changes in protein prenylation observed in KiMol cells was not caused by reduction of protein synthesis because the levels
		prenylated proteins was decreased, and the percent of bound farnesol
	www.pnas.org /cgi/content/full/95/23/13646 (4215 words)

	The Branch Point Enzyme of the Mevalonate Pathway for Protein Prenylation Is Overexpressed in the ob/ob Mouse and ...
		The Branch Point Enzyme of the Mevalonate Pathway for Protein Prenylation Is Overexpressed in the ob/ob Mouse and Induced by Adipogenesis -- Vicent et al.
		Protein prenylation is a posttranslational modification that involves covalent binding of isoprenoid lipids to conserved cysteine
		Prenylated proteins: the structure of the isoprenoid group.
	mcb.asm.org /cgi/content/full/20/6/2158 (5468 words)

	Prenylation-dependent Association of Protein-tyrosine Phosphatases PRL-1, -2, and -3 with the Plasma Membrane and the ...
		In Vitro Prenylation of Mouse PRL-1, -2, and -3-- Purified recombinant PRL proteins were incubated with HeLa cell lysates and labeled farnesyl or geranylgeranyl pyrophosphates.
		Prenylation of the PRLs is shown in the top panels, and Coomassie Blue-stained SDS-polyacrylamide gels of the purified PRL proteins are shown in the bottom panels.
		to speculate that this NLS is masked by prenylation of the adjacent
	www.jbc.org /cgi/content/full/275/28/21444 (5975 words)

	MCMP Personnel - Richard A. Gibbs
		Prenylation and the two following steps are required for the membrane association and the biological activity of Ras proteins and many other key signal transduction proteins.
		We have used the farnesylated a-factor mating peptide produced by Saccharomyces cerevisiae as a model system to evaluate the role of the prenyl group in the targeting of the prenylated protein to the proper position inside the cell and thus its biological activity.
		We have also synthesized prenylated peptides that have been used in structural studies by our collaborators at Scripps to develop a deeper understanding of the interaction of prenylated Rab proteins and the prenyl-binding protein RabGDI.
	www.mcmp.purdue.edu /faculty/?uid=rag (1069 words)

	[No title] (Site not responding. Last check: 2007-08-06)
		Protein prenylation is a widespread post-translational modification in eucaryotes and is of critical importance for the function of a number of proteins involved in oncogenesis, secretion, nuclear structure, and signal transduction.
		This compound labeled the b subunit of the enzyme suggesting that this subunit was involved in prenyl pyrophosphate binding.
		Diazotrifluoropropionates are useful for preparing photoactive prenylated peptides and proteins for investigations of the function of prenylation.
	www.chem.umn.edu /groups/distefano/Prenylation_Abstract.htm (510 words)

	3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase and Isoprenylation Inhibitors Induce Apoptosis of Vascular Smooth ...
		Effect of statins on the prenylation of Rho B. Exponentially growing rat VSMCs were exposed to increasing concentrations of several HMG-CoA reductase inhibitors (statins, 100 µmol/L for all of them) in the absence or presence of 100 µmol/L mevalonate (MVA), 5 µmol/L F-PP, or 5 µmol/L GG-PP, as indicated.
		Treatment with lipophilic statins (atorvastatin, lovastatin, and simvastatin) was associated with an attenuation of Rho B prenylation, as assessed by a reduced amount of Rho B in the membrane fractions and its appearance in the cytoplasmic fractions.
		reversal of the inhibition of Rho prenylation by mevalonate
	circres.ahajournals.org /cgi/content/full/83/5/490 (6474 words)

	Geranyltransferase
		Prenylation of proteins is a prevalent post-translational modification in eukaryotic organisms.
		It confers a lipophilic nature to the modified protein via a covalent attachment of a polyisoprenoid group, typically a farnesyl (C15) or a geranylgeranyl (C20), to the sulfhydryl group of a cysteine residue near the carboxyterminus (1,2).
		Focus on Rab prenylation increased with the observation that Hermansky-Pudlak syndrome (HPS) and the X-linked choroideremia (CHM) disease are a result of deficiences in Rab prenylation due to various mutations in the genes encoding the enzyme complex (7).
	kns.myweb.uga.edu /bcmb8010 (534 words)

	RAM2: an essential gene in the prenylation pathway of Candida albicans -- Song and White 149 (1): 249 -- Microbiology
		prenylated exogenous substrates are indicated by the arrow in
		; the prenylated endogenous substrates are the upper
		Miaczynska, M., Wagner, W., Bauer, B. E., Schweyen, R. and Ragnini, A. Ypt protein prenylation depends on the interplay among levels of Rab escort protein and geranylgeranyl diphosphate in yeast cells.
	mic.sgmjournals.org /cgi/content/full/149/1/249 (6071 words)

	Potent Suppression of Proliferation of A10 Vascular Smooth Muscle Cells by Combined Treatment with Lovastatin and ...
		Appearance of Ras in the soluble fraction of cells is presumed to reflect the inhibition of its prenylation (Gibbs et al., 1999
		Prenylation of a cysteine residue in a subset of mammalian proteins, including almost all members of the Ras superfamily of
		Khwaja A, Connolly JO and Hendry BM (2000) Prenylation inhibitors in renal disease.
	jpet.aspetjournals.org /cgi/content/full/303/1/74 (5426 words)

	Effects of Insulin on Prenylation as a Mechanism of Potentially Detrimental Influence of Hyperinsulinemia -- Draznin et ...
		Prenylated p21Ras and Rho-A were recovered in the
		and activation of the prenyl transferases (8, 9, 10).
		Cells with increased amounts of prenylated proteins have greater nuclear and other mitogenically relevant responses to other growth factors, resulting in the acceleration of several pathophysiological conditions that frequently accompany hyperinsulinemia.
	endo.endojournals.org /cgi/content/full/141/4/1310 (4458 words)

	Therapy for HDV!
		In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen.
		These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses.
		What was striking was the high level of inhibition they achieved with the prenylation inhibitors; based on RT-PCR assays the virus titers dropped at least 1,000-fold after 7 days of treatment.
	www.natap.org /2003/dec/121303_1.htm (924 words)

	The Pseudorabies Virus Us2 Protein, a Virion Tegument Component, Is Prenylated in Infected Cells -- Clase et al. 77 ...
		Prenylated proteins were immunoprecipitated from PRV Becker-infected cell extracts prepared at 5 h postinfection.
		RhoB prenylation is driven by the three carboxyl-terminal amino acids of the protein: evidenced in vivo by an anti-farnesyl cysteine antibody.
		Prenyl proteins in eukaryotic cells: a new type of membrane anchor.
	jvi.asm.org /cgi/content/full/77/22/12285 (7313 words)

	The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular ...
		Members of the Rho GTPases are subject to posttranslational modifications of prenylation, proteolysis, and carboxylmethylation.
		and prenylation occurs at a conserved cysteine in the carboxy
		Prenylation of wild-type and mutant Rac2 proteins was assessed by determining the amount of label, derived from [
	www.bloodjournal.org /cgi/content/full/100/5/1679 (5907 words)

	Structure-Activity Relationships for Inhibition of Farnesyl Diphosphate Synthase in Vitro and Inhibition of Bone ...
		Protein prenylation in purified rabbit osteoclasts in vitro was measured as described recently by Coxon et al.
		Luckman SP, Coxon FP, Ebetino FH, Russell RG and Rogers MJ (1998a) Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: Evidence from structure-activity relationships in J774 macrophages.
		Vorburger K, Kitten GT and Nigg EA (1989) Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C-terminal CXXM motif.
	jpet.aspetjournals.org /cgi/content/full/296/2/235 (6238 words)

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