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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
Ryuichiro Nakai et al.
Bioorganic & medicinal chemistry, 17(3), 1101-1108 (2008-03-28)
High-throughput screening (HTS) has become an integral part of academic and industrial efforts aimed at developing new chemical probes and drugs. These screens typically generate several 'hits', or lead active compounds, that must be prioritized for follow-up medicinal chemistry studies.
Bruce G Mockett et al.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 39(17), 3188-3203 (2019-02-26)
Secreted amyloid precursor protein-alpha (sAPPα) has growth factor-like properties and can modulate long-term potentiation (LTP) and memory. Here, we demonstrate that exposure to sAPPα converts short-lasting LTP into protein-synthesis-dependent late LTP in hippocampal slices from male rats. sAPPβ had no
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
Geoffrey A Heinzl et al.
Pharmaceutical research, 36(7), 103-103 (2019-05-19)
A rapid and broadly applicable method to assess relevant oxidative damage in biopharmaceuticals is important for lifecycle management of product quality. Multiple methods are currently employed as stress tests to induce oxidative damage for assessment of stability, safety, and efficacy.
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
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
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
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
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
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
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
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
Raffaello Verardi et al.
Structure (London, England : 1993), 25(9), 1337-1347 (2017-08-02)
DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates
Jinlong Fan et al.
Journal of materials chemistry. B, 8(33), 7501-7510 (2020-07-17)
Electrically addressable covalent immobilization of probes on a multiplexed electrode for the simultaneous detection of multiple targets within the same sample is often regarded as a difficult milestone to be achieved. Herein, we demonstrated a reagentless disposable multiplexed electrochemical DNA
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
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
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)
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
Zhanwu Hou et al.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1165, 122527-122527 (2021-01-25)
Nascent proteome presents dynamic changes in response to a certain stimulus. Thus, monitoring nascent proteome is critical to uncovering the involved biological mechanism. But the low-abundance of nascent proteome against an overwhelming pre-existing proteome limits its identification and quantification. Herein
M Sloan Siegrist et al.
ACS chemical biology, 8(3), 500-505 (2012-12-18)
Peptidoglycan (PG) is an essential component of the bacterial cell wall. Although experiments with organisms in vitro have yielded a wealth of information on PG synthesis and maturation, it is unclear how these studies translate to bacteria replicating within host
Frank Iversen et al.
Theranostics, 3(3), 201-209 (2013-03-09)
Some of the main concerns with in vivo application of naked small interfering RNA are rapid degradation and urinary excretion resulting in a short plasma half-life. In this study we investigated how conjugation of polyethylene glycol (PEG) with variable chain
Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC.
Lydia Boike et al.
Cell chemical biology, 28(1), 4-13 (2020-09-24)
MYC is a major oncogenic transcriptional driver of most human cancers that has remained intractable to direct targeting because much of MYC is intrinsically disordered. Here, we have performed a cysteine-reactive covalent ligand screen to identify compounds that could disrupt
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
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