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https://www.readbyqxmd.com/read/29753111/irak2-counterbalances-oncogenic-smurf1-in-colon-cancer-cells-by-dictating-er-stress
#1
Jingwen Liu, Yuhan Chen, Qingyang Huang, Wen Liu, Xiqing Ji, Fan Hu, Ying Zhu, Lingqiang Zhang, Guanglong Dong
The endoplasmic reticulum (ER) is a cellular organelle with central roles in maintaining proteostasis. The accumulation of misfolded proteins in the ER lumen causes ER stress. Cells evoke an evolutionarily conserved adaptive signaling network "unfolded protein response" to restore ER homeostasis, however, how the signaling network is delicately orchestrated remains largely unrevealed. Meanwhile, the HECT type E3 ligase Smad ubiquitylation regulatory factor 1 (Smurf1) has been reported to play critical roles in several important biological pathways by targeting distinct substrates for ubiquitylation, including WFS1, a critical mediator of ER stress, whereas the regulation of Smurf1 activity and abundance upon ER stress are poorly understood...
May 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29671878/targeting-autophagy-in-cancer
#2
REVIEW
Angelique V Onorati, Matheus Dyczynski, Rani Ojha, Ravi K Amaravadi
Autophagy is a conserved, self-degradation system that is critical for maintaining cellular homeostasis during stress conditions. Dysregulated autophagy has implications in health and disease. Specifically, in cancer, autophagy plays a dichotomous role by inhibiting tumor initiation but supporting tumor progression. Early results from clinical trials that repurposed hydroxychloroquine for cancer have suggested that autophagy inhibition may be a promising approach for advanced cancers. In this review of the literature, the authors present fundamental advances in the biology of autophagy, approaches to targeting autophagy, the preclinical rationale and clinical experience with hydroxychloroquine in cancer clinical trials, the potential role of autophagy in tumor immunity, and recent developments in next-generation autophagy inhibitors that have clinical potential...
April 19, 2018: Cancer
https://www.readbyqxmd.com/read/29659619/characterisation-of-two-toxoplasma-proppins-homologous-to-atg18-wipi-suggests-they-have-evolved-distinct-specialised-functions
#3
Hoa Mai Nguyen, Shuxian Liu, Wassim Daher, Feng Tan, Sébastien Besteiro
Toxoplasma gondii is a parasitic protist possessing a limited set of proteins involved in the autophagy pathway, a self-degradative machinery for protein and organelle recycling. This distant eukaryote has even repurposed part of this machinery, centered on protein ATG8, for a non-degradative function related to the maintenance of the apicoplast, a parasite-specific organelle. However, some evidence also suggest Toxoplasma is able to generate autophagic vesicles upon stress, and that some autophagy-related proteins, such as ATG9, might be involved solely in the canonical autophagy function...
2018: PloS One
https://www.readbyqxmd.com/read/29581864/galectin-3-sensitized-melanoma-cell-lines-to-vemurafenib-plx4032-induced-cell-death-through-prevention-of-autophagy
#4
Silvina Odete Bustos, Gustavo José da Silva Pereira, Renata de Freitas Saito, Cristiane Damas Gil, Daniela Bertolli Zanatta, Soraya Soubhi Smaili, Roger Chammas
Melanoma is a current worldwide problem, as its incidence is increasing. In the last years, several studies have shown that melanoma cells display high levels of autophagy, a self-degradative process that can promote survival leading to drug resistance. Consequently, autophagy regulation represents a challenge for cancer therapy. Herein, we showed that galectin-3 (Gal-3), a β-galactoside binding lectin which is often lost along melanoma progression, is a negative regulator of autophagy in melanoma cells. Our data demonstrated that Gal-3low/negative cells were more resistant to the inhibition of the activity of the cancer driver gene BRAF V600E by vemurafenib (PLX4032)...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29575706/revealing-the-self-degradation-mechanisms-in-methylammonium-lead-iodide-perovskites-stored-in-dark-and-vacuum
#5
Rajendra Kumar Gunasekaran, Deviprasath Chinnadurai, Aravindha Raja Selvaraj, Rajmohan Rajendiran, Senthil Karuppanan, Prabakar Kandasamy
Organic-inorganic lead halide perovskites phase segregates and structural degrades under illumination, exhibit poor stability with hysteresis, and produce halide accumulation at the surface. In this work, we observed the structural and interfacial dissociation in methylammonium lead iodide (CH3NH3PbI3) perovskites even in the dark and vacuum conditions. Here, we investigate the origin and consequence of self-degradation in CH3NH3PbI3 perovskites stored in the dark at vacuum. The diffraction and photoelectron spectroscopic studies reveal that the structural dissociation of perovskite into PbI2 that further dissociate into metallic lead (Pb0) and I2- ions collectively degrading perovskite stability...
March 25, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29459719/mir-142-3p-regulates-autophagy-by-targeting-atg16l1-in-thymic-derived-regulatory-t-cell-ttreg
#6
Yunjie Lu, Ji Gao, Shaopeng Zhang, Jian Gu, Hao Lu, Yongxiang Xia, Qin Zhu, Xiaofeng Qian, Feng Zhang, Chuanyong Zhang, Hongbing Shen, Keli L Hippen, Bruce R Blazar, Ling Lu, Xuehao Wang
Thymic-derived regulatory T cell (tTreg) clinical trials show therapeutic promise in the prevention of acute graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation patients. However, strategies are needed to improve tTreg proliferative ability and survival as a means to improve tTreg therapy and reduce the requirement for producing large numbers of Treg cells for adoptive tTreg transfer. Autophagy is a self-degradative process for cytosolic components, which is involved in cells death, differentiation, lymphocyte homeostasis, and tTreg function...
February 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29426521/superhydrophobic-titania-nanoparticles-for-fabrication-of-paper-based-analytical-devices-an-example-of-heavy-metals-assays
#7
Wenjian Xu, Xi Chen, Songcai Cai, Jin Chen, Zhen Xu, Hongpeng Jia, Jing Chen
A new strategy has been introduced to successfully fabricate the hydrophobic barriers of PADs by using organofluorine-modified superhydrophobic TiO2 NPs. Superhydrophobic TiO2 -140 NPs with high-photoactivity can be converted to hydrophilicity by self-degradation of surface organic moieties under full spectrum light irradiation. Superhydrophobic TiO2 -RT NPs with low-photoactivity exhibits good hydrophobic stability under light irradiation. Thus, combining these features, the PADs have been designed and constructed by photo-induced fabrication of hydrophobic barriers on the surface of the paper...
May 1, 2018: Talanta
https://www.readbyqxmd.com/read/29405978/new-insights-into-beclin-1-evolution-and-pan-malignancy-inhibitor-activity
#8
Stephen L Wechman, Anjan K Pradhan, Rob DeSalle, Swadesh K Das, Luni Emdad, Devanand Sarkar, Paul B Fisher
Autophagy is a functionally conserved self-degradation process that facilitates the survival of eukaryotic life via the management of cellular bioenergetics and maintenance of the fidelity of genomic DNA. The first known autophagy inducer was Beclin-1. Beclin-1 is expressed in multicellular eukaryotes ranging throughout plants to animals, comprising a nonmonophyllic group, as shown in this report via aggressive BLAST searches. In humans, Beclin-1 is a haploinsuffient tumor suppressor as biallelic deletions have not been observed in patient tumors clinically...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29356327/functions-of-autophagy-in-the-tumor-microenvironment-and-cancer-metastasis
#9
REVIEW
Erin E Mowers, Marina N Sharifi, Kay F Macleod
Macro-autophagy is an ancient and highly conserved self-degradative process that plays a homeostatic role in normal cells by eliminating organelles, pathogens, and protein aggregates. Autophagy, as it is routinely referred to, also allows cells to maintain metabolic sufficiency and survive under conditions of nutrient stress by recycling the by-products of autophagic degradation, such as fatty acids, amino acids, and nucleotides. Tumor cells are more reliant than normal cells on autophagy for survival in part due to their rapid growth rate, altered metabolism, and nutrient-deprived growth environment...
January 21, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29338056/context-dependent-autoprocessing-of-human-immunodeficiency-virus-type-1-protease-precursors
#10
ChihFeng Tien, Liangqun Huang, Susan M Watanabe, Jordan T Speidel, Carol A Carter, Chaoping Chen
HIV-1 protease autoprocessing is responsible for liberation of free mature protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system was previously developed to examine the autoprocessing mechanism of fusion precursors carrying the p6*-PR miniprecursor sandwiched between various proteins or epitopes. We here report that precursor autoprocessing is context-dependent as its activity and outcomes can be modulated by sequences upstream of p6*-PR. This was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP) when placed at the N-terminus of a fusion precursor...
2018: PloS One
https://www.readbyqxmd.com/read/29196289/poly-3-hydroxybutyrate-functionalization-with-biof-tagged-recombinant-proteins
#11
Daniel Bello-Gil, Beatriz Maestro, Jennifer Fonseca, Nina Dinjaski, M Auxiliadora Prieto, Jesús M Sanz
Polyhydroxyalkanoates (PHAs) are biodegradable polyesters that accumulate in the cytoplasm of certain bacteria. One promising biotechnological application utilizes these biopolymers as supports for protein immobilization. Here, the PHA-binding domain of the Pseudomonas putida KT2440 PhaF phasin (BioF polypeptide) was investigated as an affinity tag for the in vitro functionalization of poly-3-hydroxybutyrate (PHB) particles with recombinant proteins, namely, full-length PhaF and two fusion proteins tagged to BioF (BioF-C-LytA and BioF-β-galactosidase, containing the choline-binding module C-LytA and the β-galactosidase enzyme, respectively)...
February 15, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29024806/dimerization-and-oxidation-of-tryptophan-in-uv-a-photolysis-sensitized-by-kynurenic-acid
#12
Ekaterina D Sormacheva, Peter S Sherin, Yuri P Tsentalovich
Photoinduced generation of radicals in the eye lens may play an important role in the modification of proteins leading to their coloration, aggregation, and insolubilization. The radicals can be formed via the reactions of photoexcited endogenous chromophores of the human lens with lens proteins, in particular with tryptophan residues. In the present work we studied the reactions induced by UV-A (315-400nm) light between kynurenic acid (KNA), an effective photosensitizer present in the human lens, and N-acetyl-L-tryptophan (NTrpH) under aerobic and anaerobic conditions...
October 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29018234/homo-protacs-bivalent-small-molecule-dimerizers-of-the-vhl-e3-ubiquitin-ligase-to-induce-self-degradation
#13
Chiara Maniaci, Scott J Hughes, Andrea Testa, Wenzhang Chen, Douglas J Lamont, Sonia Rocha, Dario R Alessi, Roberto Romeo, Alessio Ciulli
E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28946098/high-yield-secretory-production-of-stable-active-trypsin-through-engineering-of-the-n-terminal-peptide-and-self-degradation-sites-in-pichia-pastoris
#14
Yunfeng Zhang, Hao Huang, Xinhui Yao, Guocheng Du, Jian Chen, Zhen Kang
Streptomyces griseus trypsin (SGT) possesses enzymatic properties similar to mammalian trypsins and has great potential applications in the leather processing, bioethanol, detergent and pharmaceutical industry. Here, a new strategy was reported for improving its stable, active secretory production through engineering of its propeptide and self-degradation sites. By rationally introducing hydrophobic mutations into the N-terminus of SGT Exmt (R145I), replacing the propeptide with FPVDDDDK and engineering the α-factor signal peptide, trypsin production (amidase activity) was improved to 177...
August 4, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28882757/ion-channel-functional-protein-kinase-trpm7-regulates-mg-ions-to-promote-the-osteoinduction-of-human-osteoblast-via-pi3k-pathway-in-vitro-simulation-of-the-bone-repairing-effect-of-mg-based-alloy-implant
#15
Xiuzhi Zhang, Haiyue Zu, Dewei Zhao, Ke Yang, Simiao Tian, Xiaoming Yu, Faqiang Lu, Baoyi Liu, Xiaobing Yu, Benjie Wang, Wei Wang, Shibo Huang, Yongxuan Wang, Zihua Wang, Zhaodong Zhang
Mg-based alloys, as the potential orthopaedic implant, can self-degrade to avoid second operation for its remove, and enable to promote bone repair; however, the underlying molecular mechanisms remain unclear. In the present study, we examined the effect of Mg ions on osteogenesis, chemotaxis and anti-alkaline stress in hFOB1.19 human osteoblast cells to simulate bone-repairing effect of a biodegradable Mg-based alloy implant in vitro, and explored the regulatory role of the transient receptor potential melastatin 7 (TRPM7)/phosphoinositide 3-kinase (PI3K) signalling pathway in the process of Mg ion-induced bone repair by knockdown of TRPM7 and antagonizing PI3K activity...
November 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28813167/lipophagy-maintains-energy-homeostasis-in-the-kidney-proximal-tubule-during-prolonged-starvation
#16
Satoshi Minami, Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Tomonori Kimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Yoshitaka Isaka
Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-specific Atg5-deficient (atg5-TSKO) mice and an in vitro serum starvation model...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28777374/high-mobility-group-a1-protein-modulates-autophagy-in-cancer-cells
#17
Andrea Conte, Simona Paladino, Gaia Bianco, Dominga Fasano, Raffaele Gerlini, Mara Tornincasa, Maurizio Renna, Alfredo Fusco, Donatella Tramontano, Giovanna Maria Pierantoni
High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions...
November 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28646911/autophagy-and-multidrug-resistance-in-cancer
#18
REVIEW
Ying-Jie Li, Yu-He Lei, Nan Yao, Chen-Ran Wang, Nan Hu, Wen-Cai Ye, Dong-Mei Zhang, Zhe-Sheng Chen
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal...
June 24, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28625127/the-hippocampal-autophagic-machinery-is-depressed-in-the-absence-of-the-circadian-clock-protein-per1-that-may-lead-to-vulnerability-during-cerebral-ischemia
#19
Abdalhaq Rami, Julia Fekadu, Oliver Rawashdeh
BACKGROUND: Autophagy is an intracellular bulk self-degrading process in which cytoplasmic contents of abnormal proteins and excess or damaged organelles are sequestered into autophagosomes, and degraded upon fusion with lysosomes. Although autophagy is generally considered to be pro-survival, it also functions in cell death processes. We recently reported on the hippocampal, higher vulnerability to cerebral ischemia in mice lacking the circadian clock protein PERIOD1 (PER1), a phenomenon we found to be linked to a PER1-dependent modulation of the expression patterns of apoptotic/autophagic markers...
2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28545464/c10orf10-depp-mediated-ros-accumulation-is-a-critical-modulator-of-foxo3-induced-autophagy
#20
S Salcher, M Hermann, U Kiechl-Kohlendorfer, M J Ausserlechner, P Obexer
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification...
May 25, 2017: Molecular Cancer
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