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Large-scale identification of ubiquitination sites by mass spectrometry
Udeshi ND, et al.
Nature Protocols, 8(10), 1950-1950 (2013)
Jian-Dong Ren et al.
Biochimica et biophysica acta, 1863(1), 50-55 (2015-10-22)
The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1β, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to
Garrett E Berry et al.
The Journal of biological chemistry, 291(2), 939-947 (2015-11-04)
Intracellular trafficking of viruses can be influenced by a variety of inter-connected cellular sorting and degradation pathways involving endo-lysosomal vesicles, the ubiquitin-proteasome system, and autophagy-based or endoplasmic reticulum-associated machinery. In the case of recombinant adeno-associated viruses (AAV), proteasome inhibitors are
Kazuhiko Watabe et al.
Neuropathology : official journal of the Japanese Society of Neuropathology, 40(6), 570-586 (2020-07-21)
Transactivation response DNA-binding protein of 43 kDa (TDP-43) is a major constituent of cytoplasmic aggregates in neuronal and glial cells in cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We have previously shown neuronal cytoplasmic aggregate formation
Hiroki Akiyama et al.
Cancers, 12(2) (2020-02-14)
JAK2-V617F plays a key role in the pathogenesis of myeloproliferative neoplasm. However, its inhibitor ruxolitinib has shown limited clinical efficacies because of the ruxolitinib-persistent proliferation of JAK2-V617F-positive cells. We here demonstrate that the USP9X inhibitor WP1130 or EOAI3402143 (G9) inhibited
Cytosolic iron-sulfur assembly is evolutionarily tuned by a cancer-amplified ubiquitin ligase
Weon JL, et sl.
Molecular Cell, 69(1), 113-125 (2018)
David B Beck et al.
Science advances, 7(4) (2021-02-02)
Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with
Xibao Zhao et al.
Frontiers in pharmacology, 8, 565-565 (2017-09-08)
Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here
Tyler Bland et al.
Endocrinology, 160(8), 1982-1998 (2019-06-15)
Leptin has neurotrophic actions in the hippocampus to increase synapse formation and stimulate neuronal plasticity. Leptin also enhances cognition and has antidepressive and anxiolytic-like effects, two hippocampal-dependent behaviors. In contrast, mice lacking leptin or the long form of the leptin
Hotaka Kobayashi et al.
Molecular cell, 73(1), 119-129 (2018-12-07)
MicroRNAs (miRNAs) are loaded into the Argonaute subfamily of proteins (AGO) to form an effector complex that silences target genes. Empty but not miRNA-loaded AGO is selectively degraded across species. However, the mechanism and biological significance of selective AGO degradation
Anne Garreau et al.
Journal of immunology (Baltimore, Md. : 1950), 199(8), 2758-2766 (2017-09-08)
Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4
Dominique Thevenon et al.
Frontiers in cell and developmental biology, 8, 506-506 (2020-07-09)
The c-Myc oncogene is a transcription factor that regulates the expression of a very large set of genes mainly involved in cell growth and proliferation. It is overexpressed in more than 70% of human cancers, illustrating the importance of keeping
Rudolf Lucas et al.
The Journal of biological chemistry, 291(45), 23440-23451 (2016-09-21)
Regulation of the epithelial sodium channel (ENaC), which regulates fluid homeostasis and blood pressure, is complex and remains incompletely understood. The TIP peptide, a mimic of the lectin-like domain of TNF, activates ENaC by binding to glycosylated residues in the
Yang Zhou et al.
Antonie van Leeuwenhoek, 108(1), 163-171 (2015-05-20)
Mycobacterium bovis is the causative agent of tuberculosis in cattle. Infection of macrophages with M. bovis leads to the activation of the "nucleotide binding and oligomerization, leucine-rich repeat and pyrin domains-containing protein 3" (NLRP3) and "absent in melanoma 2" (AIM2)
Bernadette Carroll et al.
Nature communications, 9(1), 256-256 (2018-01-19)
Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the
Nicholas P Boyer et al.
The Journal of cell biology, 219(1) (2019-12-11)
Appropriate axon guidance is necessary to form accurate neuronal connections. Axon guidance cues that stimulate cytoskeletal reorganization within the growth cone direct axon navigation. Filopodia at the growth cone periphery have long been considered sensors for axon guidance cues, yet
Takashi Yasukawa et al.
Cell reports, 30(10), 3478-3491 (2020-03-12)
Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by accumulations of Aβ peptides. Production and fibrillation of Aβ are downregulated by BRI2 and BRI3, which are physiological inhibitors of amyloid precursor protein (APP) processing and Aβ oligomerization. Here, we
Loss of TAX1BP1-Directed Autophagy Results in Protein Aggregate Accumulation in the Brain.
Sarraf, et al.
Molecular Cell, 80, 779-795 (2021)
Maria Stella Ritorto et al.
Nature communications, 5, 4763-4763 (2014-08-28)
Deubiquitylases (DUBs) are key regulators of the ubiquitin system which cleave ubiquitin moieties from proteins and polyubiquitin chains. Several DUBs have been implicated in various diseases and are attractive drug targets. We have developed a sensitive and fast assay to
Martin Steger et al.
Nature communications, 12(1), 5399-5399 (2021-09-15)
Mass spectrometry (MS)-based ubiquitinomics provides system-level understanding of ubiquitin signaling. Here we present a scalable workflow for deep and precise in vivo ubiquitinome profiling, coupling an improved sample preparation protocol with data-independent acquisition (DIA)-MS and neural network-based data processing specifically
Soumyadip Das et al.
Cell death and differentiation, 27(11), 3004-3020 (2020-05-18)
Conventional screening methods for deubiquitinating enzymes (DUBs) have important limitations. A loss-of-function study based on the knockout of DUB genes in mammalian cells can provide an excellent model for exploring DUB function. Here, we used CRISPR-Cas9 to perform genome-scale knockout
Hirotaka Takahashi et al.
Biomedicines, 8(6) (2020-06-10)
Protein ubiquitinations play pivotal roles in many cellular processes, including homeostasis, responses to various stimulations, and progression of diseases. Deubiquitinating enzymes (DUBs) remove ubiquitin molecules from ubiquitinated proteins and cleave the polyubiquitin chain, thus negatively regulating numerous ubiquitin-dependent processes. Dysfunctions
Alban Ordureau et al.
Molecular cell, 77(5), 1124-1142 (2020-03-07)
The ubiquitin ligase Parkin, protein kinase PINK1, USP30 deubiquitylase, and p97 segregase function together to regulate turnover of damaged mitochondria via mitophagy, but our mechanistic understanding in neurons is limited. Here, we combine induced neurons (iNeurons) derived from embryonic stem
Ian G Cowell et al.
Molecular pharmacology, 96(5), 562-572 (2019-09-14)
2,6-Diaminopyridine-3,5-bis(thiocyanate) (PR-619) is a broad-spectrum deubiquitinating enzyme (DUB) inhibitor that has been employed in cell-based studies as a tool to investigate the role of ubiquitination in various cellular processes. Here, we demonstrate that in addition to its action as a
Lilian Phu et al.
Molecular cell, 77(5), 1107-1123 (2020-03-07)
Mitochondria import nearly their entire proteome from the cytoplasm by translocating precursor proteins through the translocase of the outer membrane (TOM) complex. Here, we show dynamic regulation of mitochondrial import by the ubiquitin system. Acute pharmacological inhibition or genetic ablation
A Katherine Hatstat et al.
Cell chemical biology, 28(1), 14-25 (2020-11-12)
The benzdiimidazole NAB2 rescues α-synuclein-associated trafficking defects associated with early onset Parkinson's disease in a Nedd4-dependent manner. Despite identification of E3 ubiquitin ligase Nedd4 as a putative target of NAB2, its molecular mechanism of action has not been elucidated. As
Tomoyuki Ohsugi et al.
Oncogene, 38(32), 6051-6064 (2019-07-12)
Impaired Wnt signaling pathway plays a crucial role in the development of colorectal cancer through activation of the β-catenin/TCF7L2 complex. Although genes upregulated by Wnt/β-catenin signaling have been intensively studied, the roles of downregulated genes are poorly understood. Previously, we
Lydia Mata-Cantero et al.
Malaria journal, 14, 200-200 (2015-05-15)
The ubiquitin proteasome system (UPS) is one of the main proteolytical pathways in eukaryotic cells and plays an essential role in key cellular processes such as cell cycle, stress response, signal transduction, and transcriptional regulation. Many components of this pathway
Sajjan Koirala et al.
Cell reports, 32(3), 107922-107922 (2020-07-23)
Spatiotemporal control of Wnt/β-catenin signaling is critical for organism development and homeostasis. The poly-(ADP)-ribose polymerase Tankyrase (TNKS1) promotes Wnt/β-catenin signaling through PARylation-mediated degradation of AXIN1, a component of the β-catenin destruction complex. Although Wnt/β-catenin is a niche-restricted signaling program, tissue-specific
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