Read by QxMD icon Read

ubiquitin d

Kiran Rawat, Amit Shard, Manali Jadhav, Mayuri Gandhi, Prince Anand, Rituraj Purohit, Yogendra Padwad, Arun K Sinha
Gliomas are lethal and aggressive form of brain tumors with resistance to conventional radiation and cytotoxic chemotherapies; inviting continuous efforts for drug discovery and drug delivery. Interestingly, small molecule hybrids are one such pharmacophore that continues to capture interest owing to their pluripotent medicinal effects. Accordingly, we earlier reported synthesis of potent Styryl-cinnamate hybrids (analogues of Salvianolic acid F) along with its plausible mode of action (MOA). We explored iTRAQ-LC/MS-MS technique to deduce differentially expressed landscape of native & phospho-proteins in treated glioma cells...
December 1, 2018: Experimental Cell Research
L Bramasole, A Sinha, S Gurevich, M Radzinski, Y Klein, N Panat, E Gefen, T Rinaldi, D Jimenez-Morales, J Johnson, N J Krogan, N Reis, D Reichmann, M H Glickman, E Pick
Cycles of Cdc53/Cullin1 rubylation (a.k.a NEDDylation) protect ubiquitin-E3 SCF (Skp1-Cullin1-F-box protein) complexes from self-destruction and play an important role in mediating the ubiquitination of key protein substrates involved in cell cycle progression, development, and survival. Cul1 rubylation is balanced by the COP9 signalosome (CSN), a multi-subunit derubylase that shows 1:1 paralogy to the 26S proteasome lid. The turnover of SCF substrates and their relevance to various diseases is well studied, yet, the extent by which environmental perturbations influence Cul1 rubylation/derubylation cycles per se is still unclear...
November 17, 2018: Redox Biology
Denis Tvorogov, Daniel Thomas, Nicholas P D Liau, Mara Dottore, Emma F Barry, Maya Lathi, Winnie L Kan, Timothy R Hercus, Frank Stomski, Timothy P Hughes, Vinay Tergaonkar, Michael W Parker, David M Ross, Ravindra Majeti, Jeffrey J Babon, Angel F Lopez
Treatment of patients with myelofibrosis with the type I JAK (Janus kinase) inhibitor ruxolitinib paradoxically induces JAK2 activation loop phosphorylation and is associated with a life-threatening cytokine-rebound syndrome if rapidly withdrawn. We developed a time-dependent assay to mimic ruxolitinib withdrawal in primary JAK2V617F and CALR mutant myelofibrosis patient samples and observed notable activation of spontaneous STAT signaling in JAK2V617F samples after drug washout. Accumulation of ruxolitinib-induced JAK2 phosphorylation was dose dependent and correlated with rebound signaling and the presence of a JAK2V617F mutation...
November 2018: Science Advances
The Duy Nguyen, Shabnam Shaid, Olesya Vakhrusheva, Sebastian E Koschade, Kevin Klann, Marlyn Thöken, Fatima Baker, Jing Zhang, Thomas Oellerich, Duran Sürün, Anja Derlet, Isabella Haberbosch, Stefan Eimer, Heinz D Osiewacz, Christian Behrends, Christian Münch, Ivan Dikic, Christian H Brandts
Autophagy maintains hematopoietic stem cell integrity and prevents malignant transformation. In addition to bulk degradation, selective autophagy serves as an intracellular quality control mechanism and requires autophagy receptors such as p62 (SQSTM1) to specifically bridge the ubiquitinated cargos into autophagosomes. Here, we investigated the function of p62 in acute myeloid leukemia (AML) in vitro and in murine in vivo models of AML. Loss of p62 impaired expansion and colony-forming ability of leukemia cells and prolonged latency of leukemia development in mice...
November 29, 2018: Blood
Yu Wang, Jia-Jian Cao, Kai-Xin Wang, Xiao-Jian Xia, Kai Shi, Yan-Hong Zhou, Jing-Quan Yu, Jie Zhou
Autophagy, an innate cellular destructive mechanism, plays crucial roles in plant development and responses to stress. Although autophagy can be stimulated or suppressed by multiple molecular processes, the role of phytohormone signaling in autophagy is unclear. Here, we demonstrate that the transcripts of autophagy-related genes (ATGs) and the formation of autophagosomes are triggered by enhanced levels of brassinosteroid (BR). Furthermore, the BR-activated transcription factor brassinazole resistant 1 (BZR1), a positive regulator of the BR signaling pathway, was involved in BR-induced autophagy...
November 27, 2018: Plant Physiology
Alexis Goichon, Wafa Bahlouli, Ibtissem Ghouzali, Philippe Chan, David Vaudry, Pierre Déchelotte, Philippe Ducrotté, Moïse Coëffier
A role for immunoproteasome in the regulation of intestinal permeability has been previously suggested both in mice during water avoidance stress (WAS) and in patients with irritable bowel syndrome (IBS). Here, we provide evidence that the ubiquitin-proteasome system (UPS) contributes to the pathophysiology of IBS. Indeed, we report that colonic proteome is altered in WAS mice and that β2i subunit deficiency modifies the proteome response that is associated with a limitation of colonic hyperpermeability. Interestingly, we show specific alterations of proteins involved in UPS, mitochondrial, and energy metabolism...
November 26, 2018: Journal of Proteome Research
Guadalupe S Costa Navarro, Sabrina Amalfi, María G López, Gabriela Llauger, Joel D Arneodo, Oscar Taboga, Victoria Alfonso
No abstract text is available yet for this article.
November 22, 2018: Virus Research
Krystal K Lum, Bokai Song, Joel D Federspiel, Benjamin A Diner, Timothy Howard, Ileana M Cristea
Viral DNA sensing is an essential component of the mammalian innate immune response. Upon binding viral DNA, the cyclic-GMP-AMP synthase (cGAS) catalyzes the production of cyclic dinucleotides to induce type I interferons. However, little is known about how cGAS is homeostatically maintained or regulated upon infection. Here, we define cytoplasmic cGAS interactions with cellular and viral proteins upon herpes simplex virus type 1 (HSV-1) infection in primary human fibroblasts. We compare several HSV-1 strains (wild-type, d109, d106) that induce cytokine responses and apoptosis and place cGAS interactions in the context of temporal proteome alterations using isobaric-labeling mass spectrometry...
November 12, 2018: Cell Systems
Ahmed M Wafi, Juan Hong, Tara L Rudebush, Li Yu, Bryan T Hackfort, Han-Jun Wang, Harold D Schultz, Irving H Zucker, Lie Gao
A hallmark of chronic heart failure with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin (Cur), a Nrf2 activator, would preserve or increase exercise capacity in HF. Experiments were carried out in mice with coronary artery ligation-induced HFrEF. Cur was deliveried by a subcutaneous osmotic minipump at a dose of 50 mg/kg/day for 8 weeks...
November 21, 2018: Journal of Applied Physiology
Jason R Pitarresi, Xin Liu, Alex Avendano, Katie A Thies, Gina M Sizemore, Anisha M Hammer, Blake E Hildreth, David J Wang, Sarah A Steck, Sydney Donohue, Maria C Cuitiño, Raleigh D Kladney, Thomas A Mace, Jonathan J Chang, Christina S Ennis, Huiqing Li, Roger H Reeves, Seth Blackshaw, Jianying Zhang, Lianbo Yu, Soledad A Fernandez, Wendy L Frankel, Mark Bloomston, Thomas J Rosol, Gregory B Lesinski, Stephen F Konieczny, Denis C Guttridge, Anil K Rustgi, Gustavo Leone, Jonathan W Song, Jinghai Wu, Michael C Ostrowski
The contribution of the tumor microenvironment to pancreatic ductal adenocarcinoma (PDAC) development is currently unclear. We therefore examined the consequences of disrupting paracrine Hedgehog (HH) signaling in PDAC stroma. Herein, we show that ablation of the key HH signaling gene Smoothened ( Smo ) in stromal fibroblasts led to increased proliferation of pancreatic tumor cells. Furthermore, Smo deletion resulted in proteasomal degradation of the tumor suppressor PTEN and activation of oncogenic protein kinase B (AKT) in fibroblasts...
October 2018: Life science alliance
Anahita Shariat, Ghasem Karimzadeh, Mohammad Hassan Assareh, Javad Hadian
This study aimed to determine the response of Satureja rechingeri to water deficit by quantifying the expression of three targeted genes and four traditional reference genes using quantitative real-time PCR analysis (RT-qPCR). Drought stress was imposed by withholding water 4 months after planting. Profiling of volatile and non-volatile compounds using gas chromatography/mass spectrometry (GC/MS) and high-performance thin layer chromatography (HPTLC) showed an increasing-decreasing trend of major phenolic and terpenoid compounds such as rosmarinic and caffeic acids, carvacrole, thymol and p-Cymene...
November 2018: 3 Biotech
Chengfei Liu, Wei Lou, Joy C Yang, Liangren Liu, Cameron M Armstrong, Alan P Lombard, Ruining Zhao, Onika D V Noel, Clifford G Tepper, Hong-Wu Chen, Marc Dall'Era, Christopher P Evans, Allen C Gao
Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer...
November 16, 2018: Nature Communications
Tara Ec Condos, Karen M Dunkerley, E Aisha Freeman, Kathryn R Barber, Jacob D Aguirre, Viduth K Chaugule, Yiming Xiao, Lars Konermann, Helen Walden, Gary S Shaw
The E3 ligase parkin ubiquitinates outer mitochondrial membrane proteins during oxidative stress and is linked to early-onset Parkinson's disease. Parkin is autoinhibited but is activated by the kinase PINK1 that phosphorylates ubiquitin leading to parkin recruitment, and stimulates phosphorylation of parkin's N-terminal ubiquitin-like (pUbl) domain. How these events alter the structure of parkin to allow recruitment of an E2~Ub conjugate and enhanced ubiquitination is an unresolved question. We present a model of an E2~Ub conjugate bound to the phospho-ubiquitin-loaded C-terminus of parkin, derived from NMR chemical shift perturbation experiments...
November 16, 2018: EMBO Journal
Leah E Worton, Edith M Gardiner, Ronald Y Kwon, Leah M Downey, Brandon J Ausk, Steven D Bain, Ted S Gross
At sufficient dose, intramuscular injection of Botulinum toxin A causes muscle wasting that is physiologically consistent with surgical denervation and other types of neuromuscular dysfunction. The aim of this study was to clarify early molecular and micro-RNA alterations in skeletal muscle following Botulinum toxin A-induced muscle paralysis. Quadriceps were analyzed for changes in expression of micro- and messenger RNA and protein levels after a single injection of 0.4, 2 or 4U Botulinum toxin A (/100g body weight)...
2018: PloS One
Chunling Fu, Xuanxuan Shi, Yanqing Gong, Yan Wan, Zengtian Sun, Hengliang Shi, Zhenzhen Wang, Christian Marinaccio, John D Crispino, Kailin Xu
BACKGROUND/AIMS: Chronic Lymphocytic leukemia (CLL) is characterized by accumulation of cells in the G0/G1 phase of the cell cycle and resistance to apoptosis due to gene mutation or abnormal gene expression. In our previous study, constitutively photomorphogenic 1 (COP1) was shown to be upregulated in Binet C-phase CLL patients. Based on the negative regulation of COP1 in the repair of DNA damage, we further studied the function of COP1 in CLL cell apoptosis induced by fludarabine in vitro and in vivo...
2018: Cellular Physiology and Biochemistry
Arvin Iracheta-Vellve, Charles D Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo
Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role...
November 2018: Hepatology communications
Zhenlong Liu, Cynthia Torresilla, Yong Xiao, Phuong Trang Nguyen, Clément Caté, Karina Barbosa, Éric Rassart, Shan Cen, Steve Bourgault, Benoit Barbeau
The existence of the antisense transcript-encoded HIV-1 Antisense Protein (ASP) was recently reinforced by in silico analyses providing evidence for recent appearance of this gene in the viral genome. Our previous studies led to the detection of ASP in various cell lines by Western blot, flow cytometry and confocal microscopy analyses and reported that it induced autophagy, potentially through multimer formation. Herein, our goals were to assess autophagy induction by ASP from different clades, and to identify the implicated autophagy factors...
November 7, 2018: Journal of Virology
Breton M Asken, Russell M Bauer, Steven T DeKosky, Zachary M Houck, Charles C Moreno, Michael S Jaffee, Arthur G Weber, James R Clugston
OBJECTIVE: To describe variability in concussion biomarker concentrations collected from serum in a sample of healthy collegiate athletes, as well as report reliability metrics in a subsample of female athletes. METHODS: In this observational cohort study, β-amyloid peptide 42 (Aβ42 ), total tau, S100 calcium binding protein B (S100B), ubiquitin carboxy-terminal hydrolyzing enzyme L1 (UCH-L1), glial fibrillary acidic protein, microtubule associated protein 2, and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) serum concentrations were measured in 415 (61% male, 40% white, aged 19...
November 7, 2018: Neurology
Bhopal Mohapatra, Neha Zutshi, Wei An, Benjamin Goetz, Priyanka Arya, Timothy A Bielecki, Insha Mushtaq, Matthew D Storck, Jane L Meza, Vimla Band, Hamid Band
No abstract text is available yet for this article.
November 2, 2018: Development
Sirsendu Jana, Michael Brad Strader, Fantao Meng, Wayne Hicks, Tigist Kassa, Ivan Tarandovskiy, Silvia De Paoli, Jan Simak, Michael R Heaven, John D Belcher, Gregory M Vercellotti, Abdu I Alayash
The contribution of intracellular hemoglobin (Hb) oxidation to RBC-derived microparticle (MP) formation is poorly defined in sickle cell disease (SCD). Here we report that sickle Hb (HbS) oxidation, coupled with changes in cytosolic antioxidative proteins, is associated with membrane alterations and MP formation in homozygous Townes-sickle cell (Townes-SS) mice. Photometric and proteomic analyses confirmed the presence of high levels of Hb oxidation intermediates (ferric/ferryl) and consequent β-globin posttranslational modifications, including the irreversible oxidation of βCys93 and the ubiquitination of βLys96 and βLys145...
November 2, 2018: JCI Insight
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"