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Prenylation

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https://www.readbyqxmd.com/read/28542128/hmg-coa-reductase-promotes-protein-prenylation-and-therefore-is-indispensible-for-t-cell-survival
#1
Sonja M Lacher, Julia Bruttger, Bettina Kalt, Jean Berthelet, Krishnaraj Rajalingam, Simone Wörtge, Ari Waisman
Statins are a well-established family of drugs that lower cholesterol levels via the competitive inhibition of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). In addition, the pleiotropic anti-inflammatory effects of statins on T cells make them attractive as therapeutic drugs in T-cell-driven autoimmune disorders. Since statins do not exclusively target HMGCR and thus might have varying effects on different cell types, we generated a new mouse strain allowing for the tissue-specific deletion of HMGCR...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28536643/icariin-prevents-h2o2-induced-apoptosis-via-the-pi3k-akt-pathway-in-rat-nucleus-pulposus-intervertebral-disc-cells
#2
Xiangyu Deng, Sheng Chen, Dong Zheng, Zengwu Shao, Hang Liang, Hongzhi Hu
Icariin is a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum. This study investigated the mechanism by which icariin prevents H2O2-induced apoptosis in rat nucleus pulposus (NP) cells. NP cells were isolated from the rat intervertebral disc and they were divided into five groups after 3 passages: (A) blank control; (B) 200 μM H2O2; (C) 200 μM H2O2 + 20 μM icariin; (D) 20 μM icariin + 200 μM H2O2 + 25 μM LY294002; (E) 200 μM H2O2 + 25 μM LY294002. LY294002 is a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28530791/farnesyltransferase-mediated-delivery-of-a-covalent-inhibitor-overcomes-alternative-prenylation-to-mislocalize-k-ras
#3
Christopher J Novotny, Gregory L Hamilton, Frank McCormick, Kevan Shokat
Mutationally activated Ras is one of the most common oncogenic drivers found across all malignancies, and its selective inhibition has long been a goal in both pharma and academia. One of the oldest and most validated methods to inhibit overactive Ras signaling is by interfering with its post-translational processing and subsequent cellular localization. Previous attempts to target Ras processing led to the development of farnesyltransferase inhibitors, which can inhibit H-Ras localization but not K-Ras due to its ability to bypass farnesyltransterase inhibition though alternative prenylation by geranylgeranyltransferase...
May 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28527895/suppression-of-pmrab11-inhibits-yhv-infection-in-penaeus-monodon
#4
Akechai Kongprajug, Sakol Panyim, Chalermporn Ongvarrasopone
Yellow head virus (YHV) is one of the most serious pathogens that causes worldwide shrimp production loss. It enters the cells via clathrin-mediated endocytosis and utilizes small GTPase Rab proteins such as PmRab5 and PmRab7 for intracellular trafficking. In this study, molecular cloning and functional analysis of Rab11 during YHV infection were investigated. PmRab11 cDNA was cloned by Rapid amplification of cDNA ends (RACEs). It contained two forms of sizes 1200 and 1050 bp distinct at the 5' UTR. The coding region of PmRab11 was 645 bp, encoding 214 amino acids...
May 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28522265/screening-for-bioactive-natural-products-from-a-67-compound-library-of-glycyrrhiza-inflata
#5
Yan Lin, Yi Kuang, Kai Li, Shuang Wang, Wei Song, Xue Qiao, Gulnar Sabir, Min Ye
Licorice shows a variety of pharmacological activities. This work aims to discover bioactive natural products from one botanical source of licorice, Glycyrrhiza inflata. A total of 67 free phenolics were isolated to form a compound library. Based on the bioactivities of licorice, these compounds were screened using cell- or enzyme-based bioassay methods. A total of 11 compounds exhibited potent cytotoxic activities against three human cancer cell lines (HepG2, SW480 and MCF7), while showed little toxicity on human normal cell lines LO2 and HEK293T...
May 6, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28521569/exploring-the-biochemistry-of-the-prenylome-and-its-role-in-disease-through-proteomics-progress-and-potential
#6
Maura Brioschi, Alma Martinez Fernandez, Cristina Banfi
Protein prenylation is a ubiquitous covalent post-translational modification characterized by the addition of farnesyl or geranylgeranyl isoprenoid groups to a cysteine residue located near the carboxyl terminal of a protein. It is essential for the proper localization and cellular activity of numerous proteins, including Ras family GTPases and G-proteins. In addition to its roles in cellular physiology, the prenylation process has important implications in human diseases and in the recent years, it has become attractive target of inhibitors with therapeutic potential...
May 26, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28507944/a-survey-on-phytochemical-composition-and-biological-activity-of-zygophyllum-fabago-from-iran
#7
Saeid Yaripour, Mohammad-Reza Delnavazi, Parina Asgharian, Samira Valiyari, Saeed Tavakoli, Hossein Nazemiyeh
Purpose: Zygophyllum fabago L. (Z. fabago) is a widespread perennial herb which is used as a medicinal plant in traditional medicine of Iran, Turkey and China. The present study was a survey on phytochemical constituents and biological activities of this plant. Methods: Methanolic extract of the roots was fractionated over a C-18 pre-packed cartridge (Sep-pak) and chromatographic separation was performed on a reversed-phase preparative HPLC. Structural elucidation of the isolated compounds was carried out using UV, (1)H-NMR and 13C-NMR spectral analyses...
April 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28501703/xanthohumol-a-hop-derived-prenylated-flavonoid-promotes-macrophage-reverse-cholesterol-transport
#8
Hiroshi Hirata, Harumi Uto-Kondo, Masatsune Ogura, Makoto Ayaori, Kazusa Shiotani, Ami Ota, Youichi Tsuchiya, Katsunori Ikewaki
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [(3)H]-cholesterol-labeled macrophages...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28501347/defective-protein-prenylation-is-a-diagnostic-biomarker-of-mevalonate-kinase-deficiency
#9
Marcia A Munoz, Julie Jurczyluk, Sam Mehr, Ryan C Chai, Rob J W Arts, Angela Sheu, Chelsea McMahon, Jacqueline R Center, Davinder Singh-Grewal, Jeffrey Chaitow, Dianne E Campbell, Julian M W Quinn, Kirill Alexandrov, Zakir Tnimov, Stuart G Tangye, Anna Simon, Tri Giang Phan, Michael J Rogers
No abstract text is available yet for this article.
May 4, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28500274/combined-hmg-coa-reductase-and-prenylation-inhibition-in-treatment-of-ccm
#10
Sayoko Nishimura, Ketu Mishra-Gorur, JinSeok Park, Yulia V Surovtseva, Said M Sebti, Andre Levchenko, Angeliki Louvi, Murat Gunel
Cerebral cavernous malformations (CCMs) are common vascular anomalies that develop in the central nervous system and, more rarely, the retina. The lesions can cause headache, seizures, focal neurological deficits, and hemorrhagic stroke. Symptomatic lesions are treated according to their presentation; however, targeted pharmacological therapies that improve the outcome of CCM disease are currently lacking. We performed a high-throughput screen to identify Food and Drug Administration-approved drugs or other bioactive compounds that could effectively suppress hyperproliferation of mouse brain primary astrocytes deficient for CCM3...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28489963/the-aspergillus-fumigatus-farnesyltransferase-%C3%AE-subunit-rama-mediates-growth-virulence-and-antifungal-susceptibility
#11
Tiffany S Norton, Qusai Al Abdallah, Amy M Hill, Rachel V Lovingood, Jarrod R Fortwendel
Post-translational prenylation mechanisms, including farnesylation and geranylgeranylation, mediate both subcellular localization and protein-protein interaction in eukaryotes. The prenyltransferase complex is an αβ heterodimer in which the essential α-subunit is common to both the farnesyltransferase and the geranylgeranyltransferase type-I enzymes. The β-subunit is unique to each enzyme. Farnesyltransferase activity is an important mediator of protein localization and subsequent signaling for multiple proteins, including Ras GTPases...
May 10, 2017: Virulence
https://www.readbyqxmd.com/read/28487479/the-prenylated-rab-gtpase-receptor-pra1-f4-contributes-to-protein-exit-from-the-golgi-apparatus
#12
Myounghui Lee, Yun-Joo Yoo, Dae Heon Kim, Nguyen Hong Hanh, Yun Kwon, Inhwan Hwang
Prenylated Rab acceptor 1 (PRA1) functions in the recruitment of prenylated Rab proteins to their cognate organelles. Arabidopsis contains a large number of proteins belonging to the AtPRA1 family. However, their physiological roles remain largely unknown. Herein, we investigated the physiological role of AtPRA1.F4, a member of the AtPRA1 family. A T-DNA insertion knock-down mutant of AtPRA1.F4, atpra1.f4, was smaller in stature than parent plants and possessed shorter roots, whereas transgenic plants overexpressing HA:AtPRA1...
May 9, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28471404/trml-and-tusa-are-necessary-for-rpos-and-miaa-is-required-for-hfq-expression-in-escherichia-coli
#13
Joseph I Aubee, Morenike Olu, Karl M Thompson
Previous work demonstrated that efficient RNA Polymerase sigma S-subunit (RpoS) translation requires the N6-isopentenyladenosine i6A37 transfer RNA (tRNA) modification for UUX-Leu decoding. Here we investigate the effect of two additional tRNA modification systems on RpoS translation; the analysis was also extended to another High UUX-leucine codon (HULC) protein, Host Factor for phage Qβ (Hfq). One tRNA modification, the addition of the 2'-O-methylcytidine/uridine 34 (C/U34m) tRNA modification by tRNA (cytidine/uridine-2'O)-ribose methyltransferase L (TrmL), requires the presence of the N⁶-isopentenyladenosine 37 (i⁶A37) and therefore it seemed possible that the defect in RpoS translation in the absence of i⁶A37 prenyl transferase (MiaA) was in fact due to the inability to add the C/U34m modification to UUX-Leu tRNAs...
May 4, 2017: Biomolecules
https://www.readbyqxmd.com/read/28465253/anti-inflammatory-action-of-2-carbomethoxy-2-3-epoxy-3-prenyl-1-4-naphthoquinone-cmep-nq-suppresses-both-the-myd88-dependent-and-trif-dependent-pathways-of-tlr4-signaling-in-lps-stimulated-raw264-7-cells
#14
Hyun Ju Woo, Do Youn Jun, Ji Young Lee, Hae Sun Park, Mi Hee Woo, Sook Jahr Park, Sang Chan Kim, Chae Ha Yang, Young Ho Kim
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Rubia cordifolia L. have been widely used as a traditional herbal medicine in Northeast Asia for treatment of inflammatory diseases. AIM OF THE STUDY: To elucidate the anti-inflammatory mechanism of 2-carbomethoxy-2,3-epoxy-3- prenyl-1,4-naphthoquinone (CMEP-NQ), purified from the roots of R. cordifolia L. as the major anti-inflammatory component, in LPS-treated RAW264.7 murine macrophage cells. MATERIALS AND METHODS: Anti-inflammatory activity of CMEP-NQ was investigated in LPS-treated RAW264...
April 29, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28455256/%C3%AE-glucosidase-inhibition-by-prenylated-and-lavandulyl-compounds-from-sophora-flavescens-roots-and-in-silico-analysis
#15
Jang Hoon Kim, Chong Woon Cho, Hyo Young Kim, Kyung Tae Kim, Gug-Seoun Choi, Hyeong-Hwang Kim, In Sook Cho, Sun Jung Kwon, Seung-Kook Choi, Ju-Yeon Yoon, Seo Young Yang, Jong Seong Kang, Young Ho Kim
The enzyme α-glucosidase is a good drug target for the treatment of diabetes mellitus. Four minor flavonoids (1-4) from roots of Sophora flavescens showed the inhibitory activity, with IC50 values ranging from 11.0±0.3 to 50.6±1.3μM, toward α-glucosidase. An enzyme kinetics analysis of them revealed that the compounds 1 and 4 were non-competitive, and compounds 2 and 3 were un-competitive inhibitors. For molecular docking, 3-dimensional structure of α-glucosidase was built by homology modeling. As the result, four compounds 1-4 were confirmed to interact into common binding site of α-glucosidase...
April 26, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28454210/statins-and-pancreatic-cancer
#16
Jun Gong, Esha Sachdev, Lori A Robbins, Emily Lin, Andrew E Hendifar, Monica M Mita
Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445039/tricyclic-polyprenylated-acylphloroglucinols-from-st-john-s-wort-hypericum-perforatum
#17
Yi Guo, Na Zhang, Chunmei Chen, Jinfeng Huang, Xiao-Nian Li, Junjun Liu, Hucheng Zhu, Qingyi Tong, Jinwen Zhang, Zengwei Luo, Yongbo Xue, Yonghui Zhang
The new polyprenylated acylphloroglucinol derivatives 1-15 and the known furohyperforin (16) were isolated from the stems and leaves of Hypericum perforatum. Their structures were determined by analyses of NMR and HRESIMS data. Their absolute configurations were elucidated by a combination of electronic circular dichroism (ECD) and Rh2(OCOCF3)4-induced ECD, as well as X-ray diffraction crystallography. The new hyperforatin F (9) contains a unique acetyl functionality at C-1 of the bicyclo[3.3.1]nonane core...
April 26, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28441346/xanthones-from-the-pericarp-of-garcinia-mangostana
#18
Renyue Yang, Ping Li, Nana Li, Qian Zhang, Xue Bai, Lishuo Wang, Yiying Xiao, Lirong Sun, Quan Yang, Jian Yan
Mangosteen (Garcinia mangostana L.) is one of the most popular tropical fruits (called the "Queen of Fruits"), and is a rich source of oxygenated and prenylated xanthone derivatives. In the present work, phytochemical investigation has resulted in one new prenylated xanthone and 13 known xanthones isolated from the pericarp of G. mangostana. Their structures were established by spectroscopic data analysis, including X-ray diffraction. The new one was further tested for cytotoxic activity against seven cancer cell lines (CNE-1, CNE-2, A549, H490, PC-3, SGC-7901, U87), displaying the half maximal inhibitory concentration (IC₅0) values 3...
April 25, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28432921/gates-for-soluble-and-membrane-proteins-and-two-trafficking-systems-ift-and-lift-establish-a-dynamic-ciliary-signaling-compartment
#19
REVIEW
Victor L Jensen, Michel R Leroux
Primary cilia are microtubule-based organelles found on most mammalian cell surfaces. They possess a soluble matrix and membrane contiguous with the cell body cytosol and plasma membrane, and yet, have distinct compositions that can be modulated to enable dynamic signal transduction. Here, we discuss how specialized ciliary compartments are established using a coordinated network of gating, trafficking and targeting activities. Cilium homeostasis is maintained by a size-selective molecular mesh that limits soluble protein entry, and by a membrane diffusion barrier localized at the transition zone...
April 19, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28427808/rapid-microwave-accelerated-synthesis-and-anti-osteoporosis-activities-evaluation-of-morusin-scaffolds-and-morusignin-l-scaffolds
#20
Bing Lin, Jun-Fei Huang, Xiong-Wei Liu, Xi-Tao Ma, Xiong-Li Liu, Yi Lu, Ying Zhou, Feng-Min Guo, Ting-Ting Feng
Described herein is a facile and efficient methodology toward the synthesis of Morusin scaffolds and Morusignin L scaffolds 4-9 and 12via a novel three-step approach (Michael addition or prenylation, cyclization and cyclization) and use a rapid, microwave-accelerated cyclization as the key step. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation for anti-osteoporosis activity. These Morusin, Morusignin L and newly synthesized compounds 5b, 6a, 8e, 8f greatly exhibited the highest potency, especially at the 10(-5)mol/L (P<0...
April 9, 2017: Bioorganic & Medicinal Chemistry Letters
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