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https://www.readbyqxmd.com/read/28626006/atairp2-e3-ligase-affects-aba-and-high-salinity-responses-by-stimulating-its-atp1-sdirip1-substrate-turnover
#1
Tae Rin Oh, Jong Hum Kim, Seok Keun Cho, Moon Young Ryu, Seong Wook Yang, Woo Taek Kim
AtAIRP2 is a cytosolic RING-type E3 ubiquitin (Ub) ligase that positively regulates an ABA response in Arabidopsis (Arabidopsis thaliana). Yeast two-hybrid screening using AtAIRP2 as bait identified ATP1 (AtAIRP2 Target Protein 1) as a substrate of AtAIRP2. ATP1 was found to be identical to SDIRIP1, which was recently reported to be a negative factor in ABA signaling and a target protein of the RING E3 ligase SDIR1. ATP1 was accordingly renamed ATP1/SDIRIP1. A specific interaction between AtAIRP2 and ATP1/SDIRIP1 and ubiquitination of ATP1/SDIRIP1 by AtAIRP2 were demonstrated in vitro and in planta...
June 16, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#2
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28613983/azithromycin-attenuates-myofibroblast-differentiation-and-lung-fibrosis-development-through-proteasomal-degradation-of-nox4
#3
Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Yoichi Nakanishi, Kazuyoshi Kuwano
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor beta) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28599312/cullin-3spop-ubiquitin-e3-ligase-promotes-the-poly-ubiquitination-and-degradation-of-hdac6
#4
Yuyong Tan, Yanpeng Ci, Xiangpeng Dai, Fei Wu, Jianping Guo, Deliang Liu, Brian J North, Jirong Huo, Jinfang Zhang
The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3SPOP earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28593149/effects-of-a-proteasome-inhibitor-on-cardiomyocytes-in-a-pressure-overload-hypertrophy-rat-model-an-animal-study
#5
In-Sub Kim, Won-Min Jo
BACKGROUND: The ubiquitin-proteasome system (UPS) is an important pathway of proteolysis in pathologic hypertrophic cardiomyocytes. We hypothesize that MG132, a proteasome inhibitor, might prevent hypertrophic cardiomyopathy (CMP) by blocking the UPS. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and androgen receptor (AR) have been reported to be mediators of CMP and heart failure. This study drew upon pathophysiologic studies and the analysis of NF-κB and AR to assess the cardioprotective effects of MG132 in a left ventricular hypertrophy (LVH) rat model...
June 2017: Korean Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28588709/growth-inhibition-of-human-breast-carcinoma-cells-by-overexpression-of-regulator-of-g-protein-signaling-4
#6
Hyun-Jung Park, Seung-Hyun Kim, Dong-Oh Moon
Breast cancer remains the second largest cause of mortality in women with cancer and does not respond well to conventional therapies. Regulator of G-protein signaling 4 (RGS4) is a GTPase-activating protein of the heterotrimeric Gq and Gi proteins. Altered levels of RGS4 are reportedly linked with several human diseases, including cancer. The present study investigated whether overexpression of RGS4 inhibited the growth of human breast cancer cells. Protein expression was investigated by western blot analysis...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28580641/melatonin-reduces-endoplasmic-reticulum-stress-and-corneal-dystrophy-associated-tgfbip-through-activation-of-endoplasmic-reticulum-associated-protein-degradation
#7
Seung-Il Choi, Eunhee Lee, Begum Akuzum, Jang Bin Jeong, Yong-Sun Maeng, Tae-Im Kim, Eung Kweon Kim
Endoplasmic reticulum (ER) stress is emerging as a factor for the pathogenesis of granular corneal dystrophy type 2 (GCD2). This study was designed to investigate the molecular mechanisms underlying the protective effects of melatonin on ER stress in GCD2. Our results showed that GCD2 corneal fibroblasts were more susceptible to ER stress-induced death than were wild-type cells. Melatonin significantly inhibited GCD2 corneal cell death, caspase-3 activation, and poly (ADP-ribose) polymerase 1 cleavage caused by the ER stress inducer, tunicamycin...
June 5, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28569216/potent-and-reversible-lentiviral-vector-restriction-in-murine-induced-pluripotent-stem-cells
#8
Franziska K Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W Schott, Adrian Schwarzer, Christine Goffinet, Stephen P Goff, Axel Schambach
BACKGROUND: Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers...
May 31, 2017: Retrovirology
https://www.readbyqxmd.com/read/28566374/the-sat-protein-of-porcine-parvovirus-accelerates-viral-spreading-through-irreversible-er-stress-induction
#9
István Mészáros, Renáta Tóth, Ferenc Olasz, Peter Tijssen, Zoltán Zádori
The SAT protein of porcine parvovirus (PPV) accumulates in the endoplasmic reticulum (ER) and SAT deletion induces "slow spreading" phenotype. The in vitro comparison of the wild type Kresse strain and its SAT(-) knockout mutant revealed that prolonged cell integrity and late viral release are responsible for the slower spreading of the SAT(-) virus. During PPV infection, regardless of the presence or absence of SATp, the expression of downstream ER stress response proteins (Xbp1 and CHOP) was induced. However, in the absence of SATp, significant differences were detected in the quantity and the localization of CHOP, suggesting a role of SATp in the induction of irreversible ER stress in infected cells...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28549347/the-roles-of-ing5-in-gliomas-a-good-marker-for-tumorigenesis-and-a-potential-target-for-gene-therapy
#10
Shuang Zhao, Zhi-Juan Zhao, Hao-Yu He, Ji-Cheng Wu, Xiao-Qing Ding, Lei Yang, Ning Jia, Zhi-Jie Li, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28485891/%C3%AE-syntrophin-stabilises-catalase-to-reduce-endogenous-reactive-oxygen-species-levels-during-myoblast-differentiation
#11
Jae Yun Moon, Su Jin Choi, Cheol Ho Heo, Hwan Myung Kim, Hye Sun Kim
α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis...
May 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28484439/amino-acid-residues-68-71-contribute-to-influenza-a-virus-pb1-f2-protein-stability-and-functions
#12
Yi-Ying Cheng, Shih-Rang Yang, Ying-Ting Wang, Yu-Hsin Lin, Chi-Ju Chen
Influenza A virus PB1-F2, encoding a multi-functional protein, is regarded as a virulent gene. Variation in expression pattern and protein stability among PB1-F2 proteins derived from different strains may explain why PB1-F2 functions in a strain- and cell type-specific manner. Because the protein stability of PB1-F2 affects its biological functions, we looked for sequences important for this property. By comparing variants and chimeric of PB1-F2 proteins from A/Hong Kong/156/1997 (H5N1) and A/Puerto Rico/8/1934 (H1N1), we identified amino acid residues 68-71 affect its protein stability...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28465088/nrf2-are-signaling-provides-neuroprotection-in-traumatic-brain-injury-via-modulation-of-the-ubiquitin-proteasome-system
#13
Hui Ding, Xiaoliang Wang, Handong Wang, Lin Zhu, Qiang Wang, Yue Jia, Wuting Wei, Chenhui Zhou, Heming Wu, Ke Ding
The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway exhibits protective effects in a variety of neurological diseases. However, the role of this pathway in traumatic brain injury (TBI) is not fully understood. This study investigates whether the Nrf2-ARE pathway provides neuroprotection following TBI via regulation of the ubiquitin proteasome system (UPS), and examines the involvement of this pathway in redox homeostasis. We found that activation the Nrf2-ARE pathway can mitigate secondary brain injury induced by TBI...
April 29, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28446729/wp1130-attenuates-cisplatin-resistance-by-decreasing-p53-expression-in-non-small-cell-lung-carcinomas
#14
Xiang Wang, Ying Bao, Zhaohui Dong, Qiuqiang Chen, Huihui Guo, Charlie Xiang, Jianzhong Shao
Cisplatin-based combination chemotherapy significantly improves the survival outcomes in non-small cell lung carcinomas (NSCLCs), but drug resistance commonly contributes to disease progression and relapse. Recently, accumulating evidence has indicated that deubiquitinases (DUBs) are involved in regulating tumor cell proliferation, apoptosis, and chemoresistance. We designed this study to investigate the role of WP1130, a DUB inhibitor, in regulating cisplatin cytotoxicity in NSCLCs. After being combined with WP1130, cisplatin sensitivity was significantly increased in A549 and HCC827 cells with decreased p53 expression, inhibiting their proliferation, but not in p53-deficient NCI-H1299 cells...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438434/connective-tissue-growth-factor-decreases-mitochondrial-metabolism-through-ubiquitin-mediated-degradation-of-mitochondrial-transcription-factor-a-in-oral-squamous-cell-carcinoma
#15
Wei-Ting Lai, Yue-Ju Li, Shi-Bei Wu, Cheng-Ning Yang, Tai-Sheng Wu, Yau-Huei Wei, Yi-Ting Deng
BACKGROUND/PURPOSE: Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. METHODS: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer...
April 21, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28427998/nitric-oxide-regulated-proteolysis-of-human-cyp2b6-via-the-ubiquitin-proteasome-system
#16
Choon-Myung Lee, Shweta Tripathi, Edward T Morgan
We showed previously that rat cytochrome P450 CYP2B1 undergoes NO-dependent proteasomal degradation in response to inflammatory stimuli, and that the related human enzyme CYP2B6 is also down-regulated by NO in primary human hepatocytes. To investigate the mechanism of CYP2B6 down-regulation, we made several cell lines (HeLa and HuH7 cells) in which native CYP2B6 or CYP2B6 with a C-terminal V5 tag (CYP2B6V5) are expressed from a lentiviral vector with a cytomegalovirus promoter. Native CYP2B6 protein was rapidly down-regulated in HeLa cells within 3h of treatment with the NO donor (Z)-1-[2-(2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, while its mRNA level was not down-regulated...
April 17, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28424976/the-involvement-of-nr2b-and-tau-protein-in-mg132-induced-creb-dephosphorylation
#17
Min Xie, Yuan Li, Shao-Hui Wang, Qun-Tao Yu, Xin Meng, Xiao-Mei Liao
Transcription factor cAMP response element-binding protein (CREB) plays a critical role in memory formation. Ubiquitin-proteasome system-dependent protein degradation affects the upstream signaling pathways which regulate CREB activity. However, the molecular mechanisms of proteasome inhibition on reductive CREB activity are still unclear. The current study demonstrated that MG132-inhibited proteasome activity resulted in a dose dependence of CREB dephosphorylation at Ser133 as well as decreased phosphorylation of N-methyl-D-aspartate (NMDA) receptor subunit NR2B (Tyr1472) and its tyrosine protein kinase Fyn (Tyr416)...
June 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28419994/degradation-of-mcl-1-through-gsk-3%C3%AE-activation-regulates-apoptosis-induced-by-bufalin-in-non-small-cell-lung-cancer-h1975-cells
#18
Xiao-Hong Kang, Jing-Hang Zhang, Qing-Qin Zhang, Yan-Hui Cui, Ying Wang, Wei-Zheng Kou, Zhan-Hui Miao, Ping Lu, Li-Fang Wang, Zhen-Ye Xu, Fei Cao
BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28418925/syntenin-promotes-vegf-induced-vegfr2-endocytosis-and-angiogenesis-by-increasing-ephrin-b2-function-in-endothelial-cells
#19
Nara Tae, Suhyun Lee, Okwha Kim, Juhee Park, Sunghun Na, Jeong-Hyung Lee
Syntenin, a tandem PDZ-domain-containing scaffold protein, is involved in the regulation of diverse biological functions, including protein trafficking, exosome biogenesis, and cancer metastasis. Here, we present the first study to explore the significance of syntenin in endothelial cells. Syntenin knockdown in human umbilical vein endothelial cells (HUVECs) impaired vascular endothelial growth factor (VEGF)-mediated proliferation, migration, invasion, vascular permeability, and nitric oxide (NO) production...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412401/proteasome-inhibitor-loaded-micelles-enhance-antitumor-activity-through-macrophage-reprograming-by-nf-%C3%AE%C2%BAb-inhibition
#20
Hailiang Wu, Anqi Tao, John D Martin, Sabina Quader, Xueying Liu, Kei Takahashi, Louise Hespel, Yutaka Miura, Yoshihiro Hayakawa, Tatsuro Irimura, Horacio Cabral, Kazunori Kataoka
Macrophage reprogramming towards a tumor attacking phenotype is a promising treatment strategy, yet such strategies are scarce and it is not clear how to combine them with cytotoxic therapies that are often used to treat solid tumors. Here, we evaluate whether a micelle-encapsulated proteasome inhibitor, i.e. the peptide aldehyde drug MG132, which is cytotoxic to cancer cells, can reprogram macrophages to attack the tumor. Through in vitro studies, we demonstrated that the proteasome inhibition reduces nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling - a known promoter of tumor-supporting macrophages and chemoresistance - in both cancer cells and macrophages...
April 12, 2017: Journal of Pharmaceutical Sciences
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