Abstract:
:Autophagy is a bulk, nonspecific protein degradation pathway that is involved in the pathogenesis of cancer and neurodegenerative disease. Here, we observed that xanthohumol (XN), a prenylated chalcone present in hops (Humulus lupulus L.) and beer, modulates autophagy. By using XN-immobilized beads, valosin-containing protein (VCP) was identified as a XN-binding protein. VCP has been reported to be an essential protein for autophagosome maturation. Using an in vitro pull down assay, we showed that XN bound directly to the N domain, which is known to mediate cofactor and substrate binding to VCP. These data indicated that XN inhibited the function of VCP, thereby allowing the impairment of autophagosome maturation and resulting in the accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II). This is the first report demonstrating XN as a VCP inhibitor that binds directly to the N domain of VCP. Our finding that XN bound to and inactivated VCP not only reveals the molecular mechanism of XN-modulated autophagy but may also explain how XN exhibits various biological activities that have been reported previously.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Sasazawa Y,Kanagaki S,Tashiro E,Nogawa T,Muroi M,Kondoh Y,Osada H,Imoto Mdoi
10.1021/cb200492hsubject
Has Abstractpub_date
2012-05-18 00:00:00pages
892-900issue
5eissn
1554-8929issn
1554-8937journal_volume
7pub_type
杂志文章abstract::Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle was studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency, and neurodegeneration. Biolayer interferometry (BLI) enabled direct kinetic and thermodynamic measuremen...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b01100
更新日期:2019-05-17 00:00:00
abstract::The 3D structure of a protein is determined by the unique sequence of amino acid residues comprising the polypeptide chain. Sequence changes can cause protein misfolding, a potentially toxic phenomenon implicated in various neurodegenerative disorders. In a recent paper, translational misincorporation is proposed to b...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb6004068
更新日期:2006-10-24 00:00:00
abstract::Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those containing the estrogen receptor (ER). Indeed, inhibition of LSD1 acti...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb300108c
更新日期:2012-07-20 00:00:00
abstract::Functionally selective ligands stabilize conformations of G protein-coupled receptors (GPCRs) that induce a preference for signaling via a subset of the intracellular pathways activated by the endogenous agonists. The possibility to fine-tune the functional activity of a receptor provides opportunities to develop drug...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00493
更新日期:2017-10-20 00:00:00
abstract::Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation-in...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00315
更新日期:2016-08-19 00:00:00
abstract::A new chemical method for the traceless labeling of glycoproteins with synthetic boronic acid (BA)-tosyl probes was successfully developed. The BA moiety acts as an affinity head to direct the formation of a cyclic boronate diester with the diol groups of glycans. Following this step, the electrophilic tosyl group is ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb400631w
更新日期:2014-02-21 00:00:00
abstract::RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb4001553
更新日期:2013-07-19 00:00:00
abstract::APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb200440y
更新日期:2012-03-16 00:00:00
abstract::The quest for ever more selective kinase inhibitors as potential future drugs has yielded a large repertoire of chemical probes that are selective for specific kinase conformations. These probes have been useful tools to obtain structural snapshots of kinase conformational plasticity. Similarly, kinetic and thermodyna...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb500870a
更新日期:2015-01-16 00:00:00
abstract::Cutaneous leishmaniasis remains ignored in therapeutic drug discovery programs worldwide. This is mainly because cutaneous leishmaniasis is frequently a disease of impoverished populations in countries where funds are limited for research and patient care. However, the health burden of individuals in endemic areas man...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb400800q
更新日期:2014-03-21 00:00:00
abstract::KCNE transmembrane peptides are a family of modulatory beta-subunits that assemble with voltage-gated K+ channels, producing the diversity of potassium currents needed for proper function in a variety of tissues. Although all five KCNE transcripts have been found in cardiac and other tissues, it is unclear whether two...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/cb700089s
更新日期:2007-07-20 00:00:00
abstract::The diterpene cyclase CotB2 catalyzes the cyclization of geranylgeranyl diphosphate (GGPP) to the tricyclic cyclooctat-9-en-7-ol, which is characterized by a 5-8-5-fused ring skeleton. We have previously proposed a cyclization cascade involving a unique carbon-carbon bond rearrangement combined with multiple hydride s...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00154
更新日期:2017-06-16 00:00:00
abstract::Drug resistance continues to be a growing global problem. The efficacy of small molecule inhibitors is threatened by pools of genetic diversity in all systems, including antibacterials, antifungals, cancer therapeutics, and antivirals. Resistant variants often include combinations of active site mutations and distal "...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00370
更新日期:2019-11-15 00:00:00
abstract::Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00351
更新日期:2015-10-16 00:00:00
abstract::A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 1012 members composed of 4-20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein. On the basis of selection data, some peptides were selected for resynthesis...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00852
更新日期:2018-01-19 00:00:00
abstract::We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE p...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb500388m
更新日期:2014-11-21 00:00:00
abstract::Ubiquitin specific protease 7 (USP7) regulates the protein stability of key cellular regulators in pathways ranging from apoptosis to neuronal development, making it a promising therapeutic target. Here we used an engineered, activated variant of the USP7 catalytic domain to perform structure-activity studies of elect...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00031
更新日期:2020-06-19 00:00:00
abstract::Formylglycine (fGly) is a catalytically essential residue found almost exclusively in the active sites of type I sulfatases. Formed by post-translational oxidation of cysteine or serine side chains, this aldehyde-functionalized residue participates in a unique and highly efficient catalytic mechanism for sulfate ester...
journal_title:ACS chemical biology
pub_type: 杂志文章,评审
doi:10.1021/cb500897w
更新日期:2015-01-16 00:00:00
abstract::This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli bu...
journal_title:ACS chemical biology
pub_type: 信件
doi:10.1021/cb500475y
更新日期:2014-09-19 00:00:00
abstract::Establishing the relative configuration of a bioactive natural product represents the most challenging part in determining its structure. Residual dipolar couplings (RDCs) are sensitive probes of the relative spatial orientation of internuclear vectors. We adapted a force field structure calculation methodology to all...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.7b00281
更新日期:2017-08-18 00:00:00
abstract::Regulators of G protein signaling (RGS) proteins are key players in regulating signaling via G protein-coupled receptors. RGS proteins directly bind to the Gα-subunits of activated heterotrimeric G-proteins, and accelerate the rate of GTP hydrolysis, thereby rapidly deactivating G-proteins. Using atomistic simulations...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb400568g
更新日期:2013-12-20 00:00:00
abstract::N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer's disease. One approach to enhance the function of NMDAR is...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00913
更新日期:2017-02-17 00:00:00
abstract::The oxidative addition of nitric oxide (NO) to a thiol, S-nitrosation, is a focus of studies on cyclic guanosine monophosphate (cGMP)-independent NO signaling. S-Nitrosation of the catalytic cysteine of the caspase proteases has important effects on apoptosis and consequently has received attention. Here we report on ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb600393x
更新日期:2006-11-21 00:00:00
abstract::Angucyclines are a structurally diverse class of actinobacterial natural products defined by their varied polycyclic ring systems, which display a wide range of biological activities. We recently discovered lugdunomycin (1), a highly rearranged polyketide antibiotic derived from the angucycline backbone that is synthe...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.0c00564
更新日期:2020-09-18 00:00:00
abstract::Enzymatic transfer of the AMP portion of ATP to substrate proteins has recently been described as an essential mechanism of bacterial infection for several pathogens. The first AMPylator to be discovered, VopS from Vibrio parahemolyticus, catalyzes the transfer of AMP onto the host GTPases Cdc42 and Rac1. Modification...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb4006886
更新日期:2014-02-21 00:00:00
abstract::The abundant observation of chemical fragment information for molecular complexities is a major advantage of biological NMR analysis. Thus, the development of a novel technique for NMR signal assignment and metabolite identification may offer new possibilities for exploring molecular complexities. We propose a new sig...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.5b00894
更新日期:2016-04-15 00:00:00
abstract::Hemolysis, a process by which the destruction of red blood cells leads to the release of hemoglobin, is a critical event observed during hemolytic disorders. Under oxidative stress conditions, hemoglobin can release its heme prosthetic group, which is highly cytotoxic and can catalyze the generation of reactive oxygen...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.8b00458
更新日期:2018-08-17 00:00:00
abstract::Kinetic parameters of protein-ligand interactions are progressively acknowledged as valuable information for rational drug discovery. However, a targeted optimization of binding kinetics is not easy to achieve, and further systematic studies are necessary to increase the understanding about molecular mechanisms involv...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.6b00979
更新日期:2017-01-20 00:00:00
abstract::Several C-β-d-glucopyranosyl azoles have recently been uncovered as among the most potent glycogen phosphorylase (GP) catalytic site inhibitors discovered to date. Toward further exploring their translational potential, ex vivo experiments have been performed for their effectiveness in reduction of glycogenolysis in h...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/acschembio.9b00172
更新日期:2019-07-19 00:00:00
abstract::The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, ...
journal_title:ACS chemical biology
pub_type: 杂志文章
doi:10.1021/cb400088q
更新日期:2013-07-19 00:00:00