keyword
MENU ▼
Read by QxMD icon Read
search

Deubiquitination

keyword
https://www.readbyqxmd.com/read/28088760/usp15-regulates-dynamic-protein-protein-interactions-of-the-spliceosome-through-deubiquitination-of-prp31
#1
Tanuza Das, Joon Kyu Park, Jinyoung Park, Eunji Kim, Michael Rape, Eunice EunKyeong Kim, Eun Joo Song
Post-translational modifications contribute to the spliceosome dynamics by facilitating the physical rearrangements of the spliceosome. Here, we report USP15, a deubiquitinating enzyme, as a regulator of protein-protein interactions for the spliceosome dynamics. We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15(SART3) makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3...
January 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28088611/lactobacillus-paracasei-modulates-lps-induced-inflammatory-cytokine-release-by-monocyte-macrophages-via-the-up-regulation-of-negative-regulators-of-nf-kappab-signaling-in-a-tlr2-dependent-manner
#2
Ke-Yi Sun, Dong-Hua Xu, Chao Xie, Susan Plummer, James Tang, Xiao Fan Yang, Xiao Hui Ji
The application of the probiotic lactobacillus is suggested in the treatment of some inflammatory diseases of intestines due to its potential ability to attenuate inflammation. However, the mechanism is not completely understood. In PBMCs, Lactobacillus paracasei (L. Paracasei) down-regulated the LPS-induced production of TNF-α and IL-6. Using a macrophage-like differentiated THP-1 cell line induced by PMA, we investigated the effect of L. paracasei on the production of pro-inflammatory cytokines by monocyte-macrophages...
January 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28088524/possible-roles-of-the-transcription-factor-nrf1-nfe2l1-in-neural-homeostasis-by-regulating-the-gene-expression-of-deubiquitinating-enzymes
#3
Hiroaki Taniguchi, Shota Okamuro, Misaki Kohji, Tsuyoshi Waku, Kaori Kubo, Atsushi Hatanaka, Yimeng Sun, A M Masudul Azad Chowdhury, Akiyoshi Fukamizu, Akira Kobayashi
The transcription factor Nrf1 (NFE2L1) maintains protein homeostasis (proteostasis) by regulating the gene expression of proteasome subunits in response to proteasome inhibition. The deletion of the Nrf1 gene in neural stem/progenitor cells causes severe neurodegeneration due to the accumulation of ubiquitinated proteins in Purkinje cells and motor neurons (Nrf1 NKO mice). However, the molecular mechanisms governing this neurodegenerative process remain unclear. We demonstrate herein that the loss of Nrf1 leads to the reduced gene expression of the deubiquitinating enzymes (DUBs) but not proteasome subunits in Nrf1 NKO mice between P7 and P18...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28079137/x-ray-structure-and-enzymatic-activity-profile-of-a-core-papain-like-protease-of-mers-coronavirus-with-utility-for-structure-based-drug-design
#4
Jozlyn R Clasman, Yahira M Báez-Santos, Robert C Mettelman, Amornrat O'Brien, Susan C Baker, Andrew D Mesecar
Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28076680/regulating-the-master-regulator-controlling-ubiquitination-by-thinking-outside-the-active-site
#5
Stacey-Lynn Paiva, Sara R da Silva, Elvin D de Araujo, Patrick Thomas Gunning
The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted towards the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regulation offers the potential for greater selectivity and has demonstrated less susceptibility to acquired resistance often associated with active site inhibitors. Furthermore, the isoform diversity among E1 activating, E2 conjugating, E3 ligase and deubiquitinating (DUB) enzymes offers an ideal platform for modulating activity via allostery...
January 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28067227/cdk4-6-dependent-activation-of-dub3-regulates-cancer-metastasis-through-snail1
#6
Tongzheng Liu, Jia Yu, Min Deng, Yujiao Yin, Haoxing Zhang, Kuntian Luo, Bo Qin, Yunhui Li, Chenming Wu, Tao Ren, Yang Han, Peng Yin, JungJin Kim, SeungBaek Lee, Jing Lin, Lizhi Zhang, Jun Zhang, Somaira Nowsheen, Liewei Wang, Judy Boughey, Matthew P Goetz, Jian Yuan, Zhenkun Lou
Tumour metastasis, the spread of cancer cells from the original tumour site followed by growth of secondary tumours at distant organs, is the primary cause of cancer-related deaths and remains poorly understood. Here we demonstrate that inhibition of CDK4/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4/6; CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial-mesenchymal transition and breast cancer metastasis...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28063927/deubiquitinase-usp12-promotes-lps-induced-macrophage-responses-through-inhibition-of-i%C3%AE%C2%BAb%C3%AE
#7
Tapan Kumar Singh Nayak, Neeraja P Alamuru-Yellapragada, Kishore V L Parsa
Post translational modifications, ubiquitination and its reversal by deubiquitination play an important role in regulating innate immune system. USP12 is a poorly studied deubiquitinase reported to regulate T-cell receptor signaling however the functional role of USP12 in macrophages, the principal architects of inflammation, is unknown. Thus, in this study we probed the involvement of USP12 in macrophage mediated inflammatory responses using bacterial endotoxin, LPS, as the model system. Here, we observed that the expression of USP12 was altered in time dependent manner in LPS stimulated RAW 264...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28060376/induction-of-necroptotic-cell-death-by-viral-activation-of-the-rig-i-or-sting-pathway
#8
Suruchi N Schock, Neha V Chandra, Yuefang Sun, Takashi Irie, Yoshinori Kitagawa, Bin Gotoh, Laurent Coscoy, Astar Winoto
Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. To see how general the interplay between viruses and necroptosis is, we surveyed seven different viruses...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28057764/regulation-of-yeast-escrt-iii-membrane-scission-activity-by-the-doa4-ubiquitin-hydrolase
#9
Natalie Johnson, Matt West, Greg Odorizzi
ESCRT-III executes membrane scission during the budding of intralumenal vesicles (ILVs) at endosomes. The scission mechanism is unknown but appears to be linked to the cycle of assembly and disassembly of ESCRT-III complexes at membranes. Regulating this cycle is, therefore, expected to be important for determining the timing of ESCRT-III-mediated membrane scission. We show in Saccharomyces cerevisiae that ESCRT-III complexes are stabilized and ILV membrane scission is delayed by Doa4, which is the ubiquitin hydrolase that deubiquitinates transmembrane proteins sorted as cargoes into ILVs...
January 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28035068/otub1-stabilizes-mdmx-and-promotes-its-proapoptotic-function-at-the-mitochondria
#10
Yingxiao Chen, Yue-Gang Wang, Yuhuang Li, Xiao-Xin Sun, Mu-Shui Dai
Otub1 regulates p53 stability and activity via non-canonical inhibition of UbcH5, the MDM2 cognate ubiquitin-conjugating enzyme (E2). However, whether Otub1 regulates MDMX stability and activity is not clear. Here we report that Otub1 also suppresses MDM2-mediated MDMX ubiquitination in cells and in vitro, independently of its deubiquitinating enzyme activity. Consequently, overexpression of Otub1 markedly stabilized MDMX and increased its levels, whereas knockdown of Otub1 reduced the levels of MDMX. Interestingly, MDMX induced by Otub1 can localize to mitochondria in addition to the cytosol, enhance p53 phosphorylation at S46 (p53S46P) and promote mitochondria-mediated apoptotic pathway...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28034829/bap1-is-altered-by-copy-number-loss-mutation-and-or-loss-of-protein-expression-in-more-than-70-malignant-peritoneal-mesotheliomas
#11
Noémie Leblay, Frédéric Leprêtre, Nolwenn Le Stang, Amandine Gautier-Stein, Laurent Villeneuve, Sylvie Isaac, Denis Maillet, Françoise Galateau-Sallé, Céline Villenet, Shéhérazade Sebda, Alexandra Goracci, Graham Byrnes, James D McKay, Martin Figeac, Olivier Glehen, François-Noël Gilly, Matthieu Foll, Lynnette Fernandez-Cuesta, Marie Brevet
INTRODUCTION: Malignant mesothelioma is a deadly disease strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BAP1 is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germ-line and somatic inactivation of BAP1 is frequent in pleural mesothelioma, however, little is known about its status in peritoneal mesothelioma. METHODS: Taking advantage of the extensive French national networks MESOPATH and RENAPE, we collected biological material and clinical and epidemiological data for 46 peritoneal mesothelioma patients...
December 27, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28031360/herpes-simplex-virus-type-1-ubiquitin-specific-protease-ul36-abrogates-nf-%C3%AE%C2%BAb-activation-in-dna-sensing-signal-pathway
#12
Ruijie Ye, Chenhe Su, Haiyan Xu, Chunfu Zheng
: The DNA sensing pathway triggers innate immune responses against DNA virus infection and the NF-κB signaling plays a critical role in establishing the innate immunity. Here we report that the herpes simplex virus type 1 (HSV-1) ubiquitin-specific protease (UL36USP), which is a deubiquitinase (DUB), antagonizes the NF-κB activation, depending on its DUB activity. In this study, ectopically expressed UL36USP blocked promoter activation of interferon (IFN)-β and NF-κB induced by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING)...
December 28, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28029679/usp14-inhibitor-attenuates-cerebral-ischemia-reperfusion-induced-neuronal-injury-in-mice
#13
Jia-Wei Min, Lanhai Lü, Jessica Freeling, Doug Martin, Hongmin Wang
Stroke is associated with over-production of misfolded and aggregating proteins. However, it remains largely unclear whether enhanced removal of protein aggregates following ischemic stroke is neuroprotective. Deubiquitinating enzymes (DUBs) are a large group of proteases that regulate protein degradation. The ubiquitin-specific protease 14 (USP14) is a DUB that is associated with the proteasome and negatively regulates proteasome activity. In this study, we examined the effect of IU1, a specific small molecule inhibitor of USP14, on mouse focal cerebral ischemic stroke-induced neuronal injury in mice...
December 28, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27999174/the-histone-deubiquitinase-otld1-targets-euchromatin-to-regulate-plant-growth
#14
Ido Keren, Vitaly Citovsky
Histone monoubiquitination is associated with active chromatin and plays an important role in epigenetic regulation of gene expression in plants. Deubiquitinating enzymes remove the ubiquitin group from histones and thereby contribute to gene repression. The Arabidopsis thaliana genome encodes 50 deubiquitinases, yet only 2 of them-UBP26 and OTLD1, members of the USP/UBP (ubiquitin-specific protease and ubiquitin-binding protein) and OTU (ovarian tumor protease) deubiquitinase families-are known to target histones...
December 20, 2016: Science Signaling
https://www.readbyqxmd.com/read/27993934/cell-cycle-regulated-ubiquitination-of-tankyrase-1-by-rnf8-and-abro1-brcc36-controls-the-timing-of-sister-telomere-resolution
#15
Ekta Tripathi, Susan Smith
Timely resolution of sister chromatid cohesion in G2/M is essential for genome integrity. Resolution at telomeres requires the poly(ADP-ribose) polymerase tankyrase 1, but the mechanism that times its action is unknown. Here, we show that tankyrase 1 activity at telomeres is controlled by a ubiquitination/deubiquitination cycle depending on opposing ubiquitin ligase and deubiquitinase activities. In late S/G2 phase, the DNA damage-responsive E3 ligase RNF8 conjugates K63-linked ubiquitin chains to tankyrase 1, while in G1 phase such ubiquitin chains are removed by BRISC, an ABRO1/BRCC36-containing deubiquitinase complex...
December 19, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27993553/screening-ubiquitin-specific-protease-activities-using-chemically-synthesized-ubiquitin-and-ubiquitinated-peptides
#16
Marine Bacchi, Benjamin Fould, Magali Jullian, Aude Kreiter, Amélie Maurras, Olivier Nosjean, Thibault Coursindel, Karine Puget, Gilles Ferry, Jean A Boutin
Ubiquitin, a 76 amino acid protein, is a key component that contributes to cellular protein homeostasis. The specificity of this modification is due to a series of enzymes: ligases, attaching the ubiquitin to a lysine, and deubiquitinases, which remove it. More than a hundred of such proteins are implicated in the regulation of protein turnover. Their specificities are only partially understood. We chemically synthesized ubiquitin, attached it to lysines belonging to the protein sequences known to be ubiquitinated...
February 15, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/27986371/mechanism-of-ubiquitination-and-deubiquitination-in-the-fanconi-anemia-pathway
#17
Sylvie van Twest, Vincent J Murphy, Charlotte Hodson, Winnie Tan, Paolo Swuec, Julienne J O'Rourke, Jörg Heierhorst, Wayne Crismani, Andrew J Deans
Monoubiquitination and deubiquitination of FANCD2:FANCI heterodimer is central to DNA repair in a pathway that is defective in the cancer predisposition syndrome Fanconi anemia (FA). The "FA core complex" contains the RING-E3 ligase FANCL and seven other essential proteins that are mutated in various FA subtypes. Here, we purified recombinant FA core complex to reveal the function of these other proteins. The complex contains two spatially separate FANCL molecules that are dimerized by FANCB and FAAP100. FANCC and FANCE act as substrate receptors and restrict monoubiquitination to the FANCD2:FANCI heterodimer in only a DNA-bound form...
December 9, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27977397/atp-driven-processes-of-peroxisomal-matrix-protein-import
#18
Daniel Schwerter, Immanuel Grimm, Harald W Platta, Ralf Erdmann
In peroxisomal matrix protein import two processes directly depend on the binding and hydrolysis of ATP, both taking place at late steps of the peroxisomal import cycle. First, ATP hydrolysis is required to initiate a ubiquitin-transfer cascade to modify the import (co- )receptors. These receptors display a dual localization in the cytosol and at the peroxisomal membrane, whereas only the membrane bound fraction receives the ubiquitin modification. The second ATP-dependent process of the import cycle is carried out by the two AAA+- proteins Pex1p and Pex6p...
December 15, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27960333/synthetic-uncleavable-ubiquitinated-proteins-dissect-proteasome-deubiquitination-and-degradation-and-highlight-distinctive-fate-of-tetraubiquitin
#19
Sumeet K Singh, Indrajit Sahu, Sachitanand M Mali, Hosahalli P Hemantha, Oded Kleifeld, Michael H Glickman, Ashraf Brik
Various hypotheses have been proposed regarding how chain length, linkage type, position on substrate, and susceptibility to deubiquitinases (DUBs) affect processing of different substrates by proteasome. Here we report a new strategy for the chemical synthesis of ubiquitinated proteins to generate a set of well-defined conjugates bearing an oxime bond between the chain and the substrate. We confirmed that this isopeptide replacement is resistant to DUBs and to shaving by proteasome. Analyzing products generated by proteasomes ranked how chain length governed degradation outcome...
December 14, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27960080/a-novel-link-between-inflammation-and-cancer
#20
Yenkel Grinberg-Bleyer, Sankar Ghosh
Immune checkpoint-blockade treatments targeting PD-1/PD-L1 have revolutionized cancer therapy. Hence, understanding the regulation of PD-L1 expression has major clinical relevance. In this issue of Cancer Cell, Lim et al. report that inflammation-induced and NF-κB-driven expression of deubiquitinating enzyme CSN5 leads to PD-L1 stabilization and immune suppression in tumors.
December 12, 2016: Cancer Cell
keyword
keyword
101192
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"