Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 37 for “"Prenylation"”.
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Characterization Of Protein Prenyltransferases And Protein Prenylation In Plasmodium Falciparum
… to understand the molecular mechanism of protein prenylation in Plasmodium. The key to use of prenyltransferase inhibitors for the pharmacological intervention is a thorough understanding of the in vivo prenylation pathways in the malaria parasite. Knowledge of the physiological functions of the …
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Prenylation in cell-intrinsic innate immunity to positive-strand RNA viruses
… organelle membrane targeting through protein prenylation has on the antiviral specificity of innate immune RNA binding proteins in the context of positive-strand RNA virus infection. Since positive-strand RNA viruses use host organelle membranes to construct niches for RNA replication, we …
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Alteration of prenylation: Effect on neurite outgrowth and Rho GTPase signaling
… of lovastatin effects are due to inhibition of prenylation precursors that alter Rho GTPase localization and loading of GTP. We show here that lovastatin decreases neurite initiation and concurrently increases GTP loading of RhoA in the cytosol and decreases GTP loading of Racl associated with …
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RhoA and Rac1 prenylation: Effects on serine/threonine signaling for actin polymerization
RhoA and Rac1 are small guanosine triphosphates (GTPases) that regulate cytoskeletal rearrangements, cell polarity and axon guidance and signaling pathways. Alteration of the subcellular localization or activation of Rho GTPases is implicated in several neurological conditions. Rho GTPases are …
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Studies and applications of protein prenylation using isoprenoid analogues and site-directed mutagenesis
The site-specific enzymatic modification of proteins offers a powerful tool both for the development of new research techniques and for the development of more effective therapeutics. Protein farnesyltransferase (PFTase) is a promising tool in the field of site-specific protein modification due to …
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Prenylation-independent activation of RhoA and Rac1: Effects on localization and neurite outgrowth
… neuronal processes. Both RhoA and Rac1 require prenylation for membrane targeting, which is believed to be required for activation of these GTPases via interaction with GEFs. Meta-analyses in the early 2000's showed that people who took statins, global inhibitors of protein prenylation, have …
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REDEFINING THE SCOPE OF PRENYLATION: DISCOVERY OF “FORBIDDEN” SUBSTRATE RECOGNITION AND DEVELOPMENT OF METHODS UTILIZING PRENYLATED PROTEINS
… protein structure, activity, and localization. Prenylation is one such modification wherein a 15- or 20-carbon isoprenoid group is attached to a cysteine residue near the C-terminus of a substrate protein by one of three enzymes: protein farnesyltransferase (FTase), protein …
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Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (mpnst) Cells
<p>Prenylation pathways have been targeted via several different compounds that inhibit farnesyl transferase (FTase) and/or geranylgeranyl transferase (GGTase) enzymes in many cellular and animal models of cancer. Some of these have also been evaluated in clinical trials with limited success. …
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EXPANDING THE POTENTIAL PRENYLOME: PRENYLATION OF SHORTENED TARGET SUBSTRATES BY FTASE AND DEVELOPMENT OF FRET-BASED SYSTEM FOR DETECTING POTENTIALLY “SHUNTED” PROTEINS
<p>Protein prenylation is a posttranslational modification involving the attachment of a C15 or C20 isoprenoid group to a cysteine residue near the C-terminus of the target substrate by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase type I (GGTase-I), respectively. Both of …
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The Role of High-Density Lipoproteins and Related Pathways in Alzheimer’s Disease
… were used to investigate the role of protein prenylation in synaptic function. Prenylation is an important posttranslational lipid modification process that attaches isoprenoids (the intermediates in the cholesterol biosynthesis pathway) to target proteins. Electrophysiological/histochemical …
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Synthesis of Novel Isoprenoid Diphosphate Analogs as Chemical Tools to Investigate Protein Geranylgeranylation
<p>Many proteins require prenylation in order to be biologically functional. Some such proteins include the small Ras and Rho GTPase superfamilies, nuclear lamins A and B, and the kinesin motor proteins CENP-E and F. Prenyltransferase (PTase) inhibition is currently being explored as a possible …
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Investigating the role of zoledronate for inhibition of osteosarcoma metastasis
… can be achieved by interfering with protein prenylation, a pivotal post-translational modification necessary for Rho GTPase subcellular localization and protein-protein interactions. Zoledronate (ZOL) is a potent antiresorptive agent that definitively reduces the frequency and severity of …
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Modifying Tryptophan and Indole-Derived Compounds Using Engineered Indole Prenyltransferase Enzymes
… and other indole-derived small molecules. Prenylation alters the structure of small molecules, enhances their hydrophobicity, and subsequently alters their interaction with cell membranes and receptors. Prenylation of small molecules has been reported to increase cytotoxicity and …
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Islet Dysfunction In Diabetes
… under these conditions. Post-translational prenylation of lamins is important for their localization into the nuclear membrane, and subsequent interaction with other proteins. Our results indicate that inhibition of prenylation by simvastatin and a site-specific inhibitor of protein …
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Impact of delta-tocotrienol on human melanoma cell proliferation
… provides essential intermediates for the prenylation or dolichylation of growth-related proteins including nuclear Ras, nuclear lamins, and growth factor receptors. d-δ-tocotrienol, a post-transcriptional down-regulator of HMG CoA reductase, suppresses the proliferation of marine B16 …
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Increased Geranylgeranylated K-Ras Contributes to Antineoplastic Effects of Farnesyltransferase Inhibitors.
… cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited …
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HMGCR Pathway Mediates Cerebral-Vascular Stability and Angiogenesis in Developing Zebrafish
… rupture. These effects are likely due to reduced prenylation of Rho GTPases, evidenced by morpholino-mediated blocking of the prenylation pathway and in vivo assessment of endothelial-specific localization of cdc42, a Rho GTPase family protein. These results are in conformity with recent clinical …
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Characterization of perillyl alcohol as a cell migration-inhibiting compound
… cell migration. Finally, we examined the loss of prenylation of RhoA, a small GTPase protein involved in the formation of focal adhesions and stress fibers, and corresponding morphological changes following exposure to perillyl alcohol.
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The Development and Characterisation of a Peptide Delivery Platform to Interrogate the Anticancer Effects of Bisphosphonates
… with the RALA peptide. N-BPs inhibit the prenylation of GTPase proteins, which are responsible for cell replication, morphology and signalling, to cause cell death through apoptosis. However, the in vivo therapeutic use of bisphosphonates is limited due to low bioavailability and adverse …
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Adaptive Immunity: From Autoimmune Diseases to Neuroinflammation
… further explored the mechanistic role of protein prenylation in the regulation of eTreg cells by performing a comprehensive analysis of protein prenylation-dependent molecular signaling in eTreg-cells. Specifically, we found that Fntb drives eTreg-cell maintenance by promoting mTORC1 …
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