196 results match your criteria prenylated target

Effects of Baccharin Isolated from Brazilian Green Propolis on Adipocyte Differentiation and Hyperglycemia in Diabetic Mice.

Int J Mol Sci 2021 Jun 28;22(13). Epub 2021 Jun 28.

Research Institute for Biological Functions, Chubu University, Kasugai, Aichi 487-8501, Japan.

Propolis is a honeybee product with various biological activities, including antidiabetic effects. We previously reported that artepillin C, a prenylated cinnamic acid derivative isolated from Brazilian green propolis, acts as a peroxisome proliferator-activated receptor γ (PPARγ) ligand and promotes adipocyte differentiation. In this study, we examined the effect of baccharin, another major component of Brazilian green propolis, on adipocyte differentiation. Read More

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Engineering reversible cell-cell interactions using enzymatically lipidated chemically self-assembled nanorings.

Chem Sci 2020 Oct 26;12(1):331-340. Epub 2020 Oct 26.

Department of Chemistry, University of Minnesota Minneapolis Minnesota 55455 USA

Multicellular biology is dependent on the control of cell-cell interactions. These concepts have begun to be exploited for engineering of cell-based therapies. Herein, we detail the use of a multivalent lipidated scaffold for the rapid and reversible manipulation of cell-cell interactions. Read More

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October 2020

Grape Seed Proanthocyanidins (GSPs) Inhibit the Development of Cutaneous Squamous Cell Carcinoma by Regulating the hsa_circ_0070934/miR-136-5p/PRAF2 Axis.

Cancer Manag Res 2021 1;13:4359-4371. Epub 2021 Jun 1.

Department of Dermatology, Jiangxi Province Hospital of Integrated Chinese and Western Medicine, Nanchang, Jiangxi, 330003, People's Republic of China.

Background: Grape seed proanthocyanidins (GSPs) have been shown to inhibit the progression of many cancers, including cutaneous squamous cell carcinoma (CSCC). Circular RNA (circRNA) is a key regulator for cancer progression. However, it is unclear whether GSPs can mediate the progression of CSCC by regulating circRNA. Read More

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Microbial soluble aromatic prenyltransferases for engineered biosynthesis.

Synth Syst Biotechnol 2021 Jun 15;6(2):51-62. Epub 2021 Mar 15.

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Prenyltransferase (PTase) enzymes play crucial roles in natural product biosynthesis by transferring isoprene unit(s) to target substrates, thereby generating prenylated compounds. The prenylation step leads to a diverse group of natural products with improved membrane affinity and enhanced bioactivity, as compared to the non-prenylated forms. The last two decades have witnessed increasing studies on the identification, characterization, enzyme engineering, and synthetic biology of microbial PTase family enzymes. Read More

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Inhibiting the "Undruggable" RAS/Farnesyltransferase (FTase) Cancer Target by Manumycin-related Natural Products.

Curr Med Chem 2021 Mar 15. Epub 2021 Mar 15.

Institute of Chemistry and Biotechnology, Federal University of Alagoas, Lourival Melo Mota Avenue, 57072-970, Maceió. Brazil.

Cancer is an uncontrolled cell growth that can generate diverse types of cancer, in which these will also present a different behavior in the face of pharmacological treatment. These cancers' types are found in one of the three categories, leukemias (also named lymphomas), carcinomas, and sarcomas. In general, cancer's pathogenesis is associated with three genetic mutations, where could emerge from oncogenes, tumor suppressor genes, and/or genes responsible for regulating DNA replication. Read More

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BiP-overexpressing soybean plants display accelerated hypersensitivity response (HR) affecting the SA-dependent sphingolipid and flavonoid pathways.

Phytochemistry 2021 May 25;185:112704. Epub 2021 Feb 25.

Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, UFV, BIOAGRO/INCT-IPP, Viçosa, MG, Brazil; Laboratory of Plant Molecular Biology, Department of Biochemistry and Molecular Biology, Universidade Federal de Viçosa, BIOAGRO/INCT-IPP, Viçosa, MG, Brazil; Núcleo de Análise de Biomoléculas, NuBioMol, Universidade Federal de Viçosa, Viçosa, MG, Brazil. Electronic address:

Biotic and abiotic environmental stresses have limited the increase in soybean productivity. Overexpression of the molecular chaperone BiP in transgenic plants has been associated with the response to osmotic stress and drought tolerance by maintaining cellular homeostasis and delaying hypersensitive cell death. Here, we evaluated the metabolic changes in response to the hypersensitivity response (HR) caused by the non-compatible bacteria Pseudomonas syringae pv. Read More

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Prenylated flavonoids from Ficus hirta induces HeLa cells apoptosis via MAPK and AKT signaling pathways.

Bioorg Med Chem Lett 2021 04 18;38:127859. Epub 2021 Feb 18.

Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, People's Republic of China. Electronic address:

A pair of undescribed enantiomers, (±) ficusflavonid A (1a/1b), along with five known analogues, were isolated from the roots of Ficus hirta. Their structures were determined by the analysis of extensive spectroscopic data (including UV, IR, HRESIMS and NMR). Two enantiomers (1a and 1b) were successfully separated by chiral chromatographic column and their absolute configurations were assigned by the comparison of experimental and calculated ECD data. Read More

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Regulated cleavage of glycan strands by the murein hydrolase SagB in involves a direct interaction with LyrA (SpdC).

J Bacteriol 2021 Feb 16. Epub 2021 Feb 16.

Department of Microbiology, University of Chicago, Chicago, Illinois, USA

LyrA (SpdC), a homologue of eukaryotic CAAX proteases that act on prenylated substrates, has been implicated in the assembly of several pathways of the envelope of We described earlier the sostaphin esistance (Lyr) and taphylococcal rotein A isplay (Spd) phenotypes associated with loss of the () gene. However, a direct contribution to the assembly of pentaglycine crossbridges, the target of lysostaphin cleavage in peptidoglycan, or of Staphylococcal protein A attachment to peptidoglycan could not be attributed directly to LyrA (SpdC). These two processes are catalyzed by the Fem factors and Sortase A, respectively. Read More

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February 2021

Geranylgeranyl pyrophosphate amplifies T differentiation via increased IL-2 expression to ameliorate DSS-induced colitis.

Eur J Immunol 2021 Jun 25;51(6):1461-1472. Epub 2021 Feb 25.

College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea.

Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin-induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4 T cell, which can be observed on the complete deletion of HMG-CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T-cell homeostasis. Read More

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NOGOB receptor-mediated RAS signaling pathway is a target for suppressing proliferating hemangioma.

JCI Insight 2021 02 8;6(3). Epub 2021 Feb 8.

Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, New York, USA.

Infantile hemangioma is a vascular tumor characterized by the rapid growth of disorganized blood vessels followed by slow spontaneous involution. The underlying molecular mechanisms that regulate hemangioma proliferation and involution still are not well elucidated. Our previous studies reported that NOGOB receptor (NGBR), a transmembrane protein, is required for the translocation of prenylated RAS from the cytosol to the plasma membrane and promotes RAS activation. Read More

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February 2021

Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus.

J Nat Prod 2020 10 23;83(10):2996-3003. Epub 2020 Sep 23.

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China.

This project was focused on the discovery of novel compounds that promote endogenous β-cell regeneration. Screening of extracts identified the fungus as a promising candidate. After fermentation and extraction of , we isolated five new prenylated xanthones, namely, staprexanthones A-E (-), with staprexanthone A () being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety. Read More

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October 2020

Usefulness of bile as a biomarker via ferroptosis and cysteine prenylation in cholangiocarcinoma; role of diagnosis and differentiation from benign biliary disease.

Surg Oncol 2020 Sep 23;34:174-181. Epub 2020 Apr 23.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, South Korea.

Background: Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract with a poor prognosis. Herein, we investigated possible mechanism of extrahepatic CCA (eCCA) by dysregulated iron metabolism and post-translational modifications (PTMs). Further, we evaluated potential biomarkers in the bile fluid for diagnosis of eCCA and differentiation between eCCA and benign biliary disease. Read More

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September 2020

Neuroprotective effects of prenylated flavanones isolated from Dalea species, in vitro and in silico studies.

Eur J Med Chem 2020 Nov 12;206:112718. Epub 2020 Aug 12.

Departamento de Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Montevideo, Uruguay; Laboratorio de Biofármacos, Instituto Pasteur de Montevideo, Montevideo, Uruguay. Electronic address:

Neurodegenerative diseases (NDs) represent a global problem on public health, with a growing incidence as human longevity increases. Currently, although there are palliative strategies available for most of these diseases, there is a lack of effective therapies for their cure. Flavonoids are extensively studied for their multi-target behavior. Read More

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November 2020

Synthesis of Novel Stilbene-Coumarin Derivatives and Antifungal Screening of -Specialized Metabolites Against .

Antibiotics (Basel) 2020 Aug 25;9(9). Epub 2020 Aug 25.

School of Chemistry, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.

is one of the most toxigenic phytopathogens causing diseases and reduced agricultural productivity worldwide. Current chemical fungicides exhibit toxicity against non-target organisms, triggering negative environmental impact, and are a danger to consumers. In order to explore the chemical diversity of plants for potential antifungal applications, crude extract and fractions from were screened for their activity against two multi-resistant strains: and . Read More

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Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth.

Dev Cell 2020 06 12;53(6):691-705.e7. Epub 2020 Jun 12.

Department of Biology, Johns Hopkins University, 3400 N. Charles St, 227 Mudd Hall, Baltimore, MD 21218, USA. Electronic address:

Compartmentalized signaling is critical for cellular organization and specificity of functional outcomes in neurons. Here, we report that post-translational lipidation of newly synthesized proteins in axonal compartments allows for short-term and autonomous responses to extrinsic cues. Using conditional mutant mice, we found that protein prenylation is essential for sympathetic axon innervation of target organs. Read More

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Coordination of Rheb lysosomal membrane interactions with mTORC1 activation.

F1000Res 2020 27;9. Epub 2020 May 27.

Department of Cell Biology, Yale University School of Medicine, New Haven, CT, 06510, USA.

A complex molecular machinery converges on the surface of lysosomes to ensure that the growth-promoting signaling mediated by mechanistic target of rapamycin complex 1 (mTORC1) is tightly controlled by the availability of nutrients and growth factors. The final step in this activation process is dependent on Rheb, a small GTPase that binds to mTOR and allosterically activates its kinase activity. Here we review the mechanisms that determine the subcellular localization of Rheb (and the closely related RhebL1 protein) as well as the significance of these mechanisms for controlling mTORC1 activation. Read More

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Xanthohumol Inhibits the Growth of Keratin 18-Overexpressed Esophageal Squamous Cell Carcinoma and .

Front Cell Dev Biol 2020 19;8:366. Epub 2020 May 19.

Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death worldwide. Xanthohumol is a prenylated flavonoid isolated from . Although xanthohumol has been reported to exert anti-obesity, hypoglycemic, anti-hyperlipidemia and anti-cancer activities, the mechanisms underlying its chemotherapeutic activity are yet to be elucidated. Read More

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Xanthohumol regulates miR-4749-5p-inhibited RFC2 signaling in enhancing temozolomide cytotoxicity to glioblastoma.

Life Sci 2020 Aug 16;254:117807. Epub 2020 May 16.

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taiwan; Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taiwan. Electronic address:

Aims: Xanthohumol (XN), a natural prenylated flavonoid isolated from Humulus lupulus L. (hops), possess the therapeutic effects in glioblastoma multiforme (GBM), which is a grade IV aggressive glioma in adults. However, low bioavailability and extractive yield limit the clinical applications of XN. Read More

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Morusin exerts anti-cancer activity in renal cell carcinoma by disturbing MAPK signaling pathways.

Ann Transl Med 2020 Mar;8(6):327

Department of Urology, Second Affiliated Hospital, Army Military Medical University, Chongqing 400037, China.

Background: Renal cell carcinoma (RCC) has gradually become a severe type of kidney malignant tumor, which warrants an urgent need for highly efficacious therapeutic agents. Morusin, a typical prenylated flavonoid, has been revealed to possess anticarcinogenic effects against several cancers by inhibiting cell proliferation and tumorigenesis.

Methods: Cells proliferation was examined by CCK-8. Read More

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A Non-Canonical Calmodulin Target Motif Comprising a Polybasic Region and Lipidated Terminal Residue Regulates Localization.

Int J Mol Sci 2020 Apr 15;21(8). Epub 2020 Apr 15.

Princess Margaret Cancer Centre, University Health Network, 101 College St., Toronto, ON M5G 1L7, Canada.

Calmodulin (CaM) is a Ca-sensor that regulates a wide variety of target proteins, many of which interact through short basic helical motifs bearing two hydrophobic 'anchor' residues. CaM comprises two globular lobes, each containing a pair of EF-hand Ca-binding motifs that form a Ca-induced hydrophobic pocket that binds an anchor residue. A central flexible linker allows CaM to accommodate diverse targets. Read More

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Involvement of mTOR-related signaling in antidepressant effects of Sophoraflavanone G on chronically stressed mice.

Phytother Res 2020 Sep 3;34(9):2246-2257. Epub 2020 Apr 3.

Faculty of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing, China.

SophoraflavanoneG (SG), an important prenylated flavonoid isolated from Sophoraalopecuroides.L, is effective for many illnesses. The present study was designed to investigate whether the compound could reverse depressive-like symptoms and investigate its possible mechanisms. Read More

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September 2020

Ste24: An Integral Membrane Protein Zinc Metalloprotease with Provocative Structure and Emergent Biology.

J Mol Biol 2020 08 19;432(18):5079-5090. Epub 2020 Mar 19.

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA. Electronic address:

Ste24, an integral membrane protein zinc metalloprotease, is found in every kingdom of eukaryotes. It was discovered approximately 20 years ago by yeast genetic screens identifying it as a factor responsible for processing the yeast mating a-factor pheromone. In animals, Ste24 processes prelamin A, a component of the nuclear lamina; mutations in the human ortholog of Ste24 diminish its activity, giving rise to genetic diseases of accelerated aging (progerias). Read More

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Protein Farnesyltransferase Catalyzes Unanticipated Farnesylation and Geranylgeranylation of Shortened Target Sequences.

Biochemistry 2020 03 10;59(11):1149-1162. Epub 2020 Mar 10.

Department of Chemistry, Syracuse University, Syracuse, New York 13244, United States.

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 these protein prenyltransferases recognize a C-terminal "CaaX" sequence in their protein substrates, but recent studies in yeast- and mammalian-based systems have demonstrated FTase can also accept sequences that diverge in length from the canonical four-amino acid motif, such as the recently reported five-amino acid C(x)X motif. In this work, we further expand the substrate scope of FTase by demonstrating sequence-dependent farnesylation of shorter three-amino acid "Cxx" C-terminal sequences using both genetic and biochemical assays. Read More

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Kushenol E inhibits autophagy and impairs lysosomal positioning via VCP/p97 inhibition.

Biochem Pharmacol 2020 05 17;175:113861. Epub 2020 Feb 17.

Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, South Korea; Department of Biomolecular Science, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34141, South Korea. Electronic address:

Autophagy plays a major role in cell survival and has therefore been exploited as an important strategy in cancer therapy. In this study, we evaluated the autophagy-regulatory effects of kushenol E (KE), a bi-prenylated flavonoid isolated from Sophora flavescens and found that KE increased LC3B-II levels while inducing the formation of autophagic vacuoles and immature autophagosomes in HeLa and HCT116 cells. Transmission electron microscopy images revealed that KE treatment generates immature autophagosomes. Read More

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Regulation of Small GTPase Prenylation in the Nervous System.

Mol Neurobiol 2020 May 27;57(5):2220-2231. Epub 2020 Jan 27.

Texas Woman's University, Denton, TX, USA.

Mevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. Read More

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Promising Potential of against South American Myasis.

Plants (Basel) 2019 Dec 25;9(1). Epub 2019 Dec 25.

Área de Botánica, Facultad de Ciencias, Universidad de Extremadura, Avda. Elvas s/n, 06071 Badajoz, Spain.

Traditional medicine is especially important in the treatment of neglected tropical diseases because it is the way the majority of populations of affected countries manage primary healthcare. We present a case study that can serve as an example that can be replicated by others in the same situation. It is about the validation of a local remedy for myasis in Amazonian Ecuador, which is contrasted by bibliographic chemical reviews and in silico activity tests. Read More

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December 2019

Formation of Prenylated Chalcone Xanthohumol Cocrystals: Single Crystal X-Ray Diffraction, Vibrational Spectroscopic Study Coupled with Multivariate Analysis.

Molecules 2019 Nov 21;24(23). Epub 2019 Nov 21.

Department of General and Coordination Chemistry and Crystallography, Institute of Chemical Sciences, Maria Curie-Sklodowska University in Lublin, pl. Marii Curie-Skłodowskiej 2, 20-031 Lublin, Poland.

Four novel xanthohumol (XN) cocrystals with pharmaceutically acceptable coformers, such as nicotinamide (NIC), glutarimide (GA), acetamide (AC), and caffeine (CF) in the 1:1 stoichiometry were obtained by the slow evaporation solution growth technique. The structure of the cocrystals was determined by single crystal X-ray diffraction. The analysis of packing and interactions in the crystal lattice revealed that molecules in the target cocrystals were packed into almost flat layers, formed by the O-HO, O-HN, and N-HO-type contacts between the xanthohumol and coformer molecules. Read More

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November 2019

PI3K-AKT Signaling Activation and Icariin: The Potential Effects on the Perimenopausal Depression-Like Rat Model.

Molecules 2019 Oct 15;24(20). Epub 2019 Oct 15.

Microbiology and Immunology Department, New York Medical College, Valhalla, NY 10595, USA.

Icariin is a prenylated flavonol glycoside isolated from Epimedium herb, and has been shown to be its main bioactive component. Recently, the antidepressant-like mechanism of icariin has been increasingly evaluated and demonstrated. However, there are few studies that have focused on the involvement of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (AKT) signaling in mediating the perimenopausal depression effects of icariin. Read More

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October 2019

Emerging Role of Migration and Invasion Enhancer 1 (MIEN1) in Cancer Progression and Metastasis.

Front Oncol 2019 4;9:868. Epub 2019 Sep 4.

Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, India.

Tumor metastasis is a sequential event accounting for numerous cancer-related fatalities worldwide. The process of metastasis serially involves invasion, intravasation, extravasation, and tumor growth at the secondary site. Migration and invasion enhancer 1 (MIEN1) is a membrane associated protein overexpressed in various human cancers. Read More

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September 2019

Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions.

Nat Commun 2019 09 4;10(1):3975. Epub 2019 Sep 4.

Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, SE-405 30, Gothenburg, Sweden.

Rho family proteins are prenylated by geranylgeranyltransferase type I (GGTase-I), which normally target proteins to membranes for GTP-loading. However, conditional deletion of GGTase-I in mouse macrophages increases GTP-loading of Rho proteins, leading to enhanced inflammatory responses and severe rheumatoid arthritis. Here we show that heterozygous deletion of the Rho family gene Rac1, but not Rhoa and Cdc42, reverses inflammation and arthritis in GGTase-I-deficient mice. Read More

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September 2019