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Tilman Läppchen et al.
European journal of medicinal chemistry, 89, 279-295 (2014-12-03)
Calixarene 0118 is a potent anti-angiogenic agent that effectively inhibited tumor growth in preclinical studies, and is currently being evaluated in a phase I clinical trial. We have designed two close mimetics of calixarene 0118 containing a terminal alkynyl-functional group
Qi Li et al.
Cell stem cell, 26(5), 675-692 (2020-04-08)
Intestinal homeostasis is tightly regulated by complex yet poorly understood signaling networks. Here, we demonstrate that Lats1/2, the core Hippo kinases, are essential to maintain Wnt pathway activity and intestinal stem cells. Lats1/2 deletion leads to loss of intestinal stem
Mark F van Delft et al.
Nature chemical biology, 15(11), 1057-1066 (2019-10-09)
Activating the intrinsic apoptosis pathway with small molecules is now a clinically validated approach to cancer therapy. In contrast, blocking apoptosis to prevent the death of healthy cells in disease settings has not been achieved. Caspases have been favored, but
Min Jiang et al.
The Journal of biological chemistry, 294(36), 13487-13501 (2019-07-25)
Junctophilins (JPH1-JPH4) are expressed in excitable and nonexcitable cells, where they tether endoplasmic/sarcoplasmic reticulum (ER/SR) and plasma membranes (PM). These ER/SR-PM junctions bring Ca-release channels in the ER/SR and Ca as well as Ca-activated K channels in the PM to
Wei Wang et al.
Cell host & microbe, 27(4), 601-613 (2020-04-10)
Plants deploy a variety of secondary metabolites to fend off pathogen attack. Although defense compounds are generally considered toxic to microbes, the exact mechanisms are often unknown. Here, we show that the Arabidopsis defense compound sulforaphane (SFN) functions primarily by
Pornpun Aramsangtienchai et al.
The Journal of biological chemistry, 292(13), 5325-5334 (2017-02-16)
Junctional adhesion molecule C (JAM-C) is an immunoglobulin superfamily protein expressed in epithelial cells, endothelial cells, and leukocytes. JAM-C has been implicated in leukocyte transendothelial migration, angiogenesis, cell adhesion, cell polarity, spermatogenesis, and metastasis. Here, we show that JAM-C undergoes
Keli Chai et al.
Viruses, 13(1) (2020-12-31)
Membrane proteins of enveloped viruses have been reported to undergo palmitoylation, a post-translational modification often having a critical role in the function of these viral proteins and hence viral replication. In this study, we report that the foamy virus (FV)
Neha Chauhan et al.
Yeast (Chichester, England), 37(1), 15-25 (2019-11-24)
Ergosterol is a prominent component of the yeast plasma membrane and essential for yeast cell viability. It is synthesized in the endoplasmic reticulum and transported to the plasma membrane by nonvesicular mechanisms requiring carrier proteins. Oxysterol-binding protein homologues and yeast
Shaimaa M Aboukhatwa et al.
ChemMedChem, 14(11), 1096-1107 (2019-03-29)
Histone deacetylase (HDAC) activity is modulated in vivo by post-translational modifications and formation of multiprotein complexes. Novel chemical tools to study how these factors affect engagement of HDAC isoforms by HDAC inhibitors (HDACi) in cells and tissues are needed. In this
Migle Tomkuviene et al.
Nucleic acids research, 40(14), 6765-6773 (2012-05-09)
Biophysical and mechanistic investigation of RNA function requires site-specific incorporation of spectroscopic and chemical probes, which is difficult to achieve using current technologies. We have in vitro reconstituted a functional box C/D small ribonucleoprotein RNA 2'-O-methyltransferase (C/D RNP) from the
Young-Chan Kim et al.
Nature chemical biology, 15(9), 907-916 (2019-08-21)
Toll-like receptor (TLR)/myeloid differentiation primary response protein (MYD88) signaling aggravates sepsis by impairing neutrophil migration to infection sites. However, the role of intracellular fatty acids in TLR/MYD88 signaling is unclear. Here, inhibition of fatty acid synthase by C75 improved neutrophil
Beatriz Alvarez-Castelao et al.
Nature protocols, 14(2), 556-575 (2019-01-06)
A big challenge in proteomics is the identification of cell-type-specific proteomes in vivo. This protocol describes how to label, purify and identify cell-type-specific proteomes in living mice. To make this possible, we created a Cre-recombinase-inducible mouse line expressing a mutant
Thomas W Hanigan et al.
Cell chemical biology, 24(11), 1356-1367 (2017-09-26)
Histone deacetylase (HDAC) catalytic activity is regulated by formation of co-regulator complexes and post-translational modification. Whether these mechanisms are transformed in cancer and how this affects the binding and selectivity of HDAC inhibitors (HDACis) is unclear. In this study, we
Jung-Hyun Choi et al.
The EMBO journal, 37(5) (2018-02-15)
In neuronal development, dynamic rearrangement of actin promotes axonal growth cone extension, and spatiotemporal translation of local mRNAs in response to guidance cues directs axonal growth cone steering, where cofilin plays a critical role. While regulation of cofilin activity is
Saskia Heybrock et al.
Nature communications, 10(1), 3521-3521 (2019-08-08)
The intracellular transport of cholesterol is subject to tight regulation. The structure of the lysosomal integral membrane protein type 2 (LIMP-2, also known as SCARB2) reveals a large cavity that traverses the molecule and resembles the cavity in SR-B1 that
Yi-Jia Li et al.
Cell chemical biology, 26(2), 278-288 (2018-12-26)
Ubiquitin-like (Ubl) post-translational modifications are potential targets for therapeutics. However, the only known mechanism for inhibiting a Ubl-activating enzyme is through targeting its ATP-binding site. Here we identify an allosteric inhibitory site in the small ubiquitin-like modifier (SUMO)-activating enzyme (E1). This
Eliot Morrison et al.
Communications biology, 3(1), 368-368 (2020-07-12)
Palmitoylation is the reversible addition of palmitate to cysteine via a thioester linkage. The reversible nature of this modification makes it a prime candidate as a mechanism for regulating signal transduction in T-cell receptor signaling. Following stimulation of the T-cell
Jung-Hyun Choi et al.
Molecular and cellular biology, 39(4) (2018-11-28)
Fragile X syndrome (FXS) caused by loss of fragile X mental retardation protein (FMRP), is the most common cause of inherited intellectual disability. Numerous studies show that FMRP is an RNA binding protein that regulates translation of its binding targets
Mathias J Gerl et al.
PloS one, 11(4), e0153009-e0153009 (2016-04-23)
Cell membranes contain hundreds to thousands of individual lipid species that are of structural importance but also specifically interact with proteins. Due to their highly controlled synthesis and role in signaling events sphingolipids are an intensely studied class of lipids.
Teresa Galán et al.
Biosensors & bioelectronics, 74, 751-756 (2015-07-27)
Here we describe a label-free electrochemical DNA sensor based on poly(3,4-ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene-terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence, was immobilized onto azido-derivatized conducting PEDOT electrodes using "click" chemistry. DNA hybridization was then detected
Rory K Morgan et al.
ACS chemical biology, 10(8), 1778-1784 (2015-05-16)
ADP-ribosylation is essential for cell function, yet there is a dearth of methods for detecting this post-translational modification in cells. Here, we describe a clickable aminooxy alkyne (AO-alkyne) probe that can detect cellular ADP-ribosylation on acidic amino acids following Cu-catalyzed
Susie J Zoltewicz et al.
ASN neuro, 4(6), 409-421 (2012-11-07)
PMP22 (peripheral myelin protein 22), also known as GAS 3 (growth-arrest-specific protein 3), is a disease-linked tetraspan glycoprotein of peripheral nerve myelin and constituent of intercellular junctions in epithelia. To date, our knowledge of the post-translational modification of PMP22 is
Clive Yik-Sham Chung et al.
Nature chemical biology, 15(8), 776-785 (2019-07-10)
Autophagy is a lysosomal degradation pathway that eliminates aggregated proteins and damaged organelles to maintain cellular homeostasis. A major route for activating autophagy involves inhibition of the mTORC1 kinase, but current mTORC1-targeting compounds do not allow complete and selective mTORC1
Yuanhui Ma et al.
Nature protocols, 13(8), 1744-1762 (2018-07-25)
Measuring proteome response to perturbations is critical for understanding the underlying mechanisms involved. Traditional quantitative proteomic methods are limited by the large numbers of proteins in the proteome and the mass spectrometer's dynamic range. A previous method uses the biorthogonal
Chayasith Uttamapinant et al.
Nature protocols, 8(8), 1620-1634 (2013-07-28)
This protocol describes an efficient method to site-specifically label cell-surface or purified proteins with chemical probes in two steps: probe incorporation mediated by enzymes (PRIME) followed by chelation-assisted copper-catalyzed azide-alkyne cycloaddition (CuAAC). In the PRIME step, Escherichia coli lipoic acid
Michal Segal et al.
Biology open, 1(3), 220-231 (2012-12-06)
Bidirectional transport is a key issue in cellular biology. It requires coordination between microtubule-associated molecular motors that work in opposing directions. The major retrograde and anterograde motors involved in bidirectional transport are cytoplasmic dynein and conventional kinesin, respectively. It is
Daniel T Cohen et al.
Cell reports, 30(10), 3229-3239 (2020-03-12)
BCL-2 family proteins converge at the mitochondrial outer membrane to regulate apoptosis and maintain the critical balance between cellular life and death. This physiologic process is essential to organism homeostasis and relies on protein-protein and protein-lipid interactions among BCL-2 family
Brent R Martin
Current protocols in protein science, 73, 14-14 (2014-02-11)
Methods to study protein S-palmitoylation dynamics have previously relied on metabolic labeling with [(14)C]palmitate, which requires additional safety precautions and long exposures. Nonradioactive alkynyl palmitate analogs have been developed for in-gel fluorescence detection and affinity purification. Cells metabolically labeled with
Lien Nguyen et al.
Neuron, 105(4), 645-662 (2019-12-14)
The intronic C9orf72 G4C2 expansion, the most common genetic cause of ALS and FTD, produces sense- and antisense-expansion RNAs and six dipeptide repeat-associated, non-ATG (RAN) proteins, but their roles in disease are unclear. We generated high-affinity human antibodies targeting GA
Sima Rahimian et al.
Biomaterials, 37, 469-477 (2014-12-03)
Particulate antigen delivery systems aimed at the induction of antigen-specific T cells form a promising approach in immunotherapy to replace pharmacokinetically unfavorable soluble antigen formulations. In this study, we developed a delivery system using the model protein antigen ovalbumin (OVA)
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