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https://www.readbyqxmd.com/read/29328425/bioinformatics-analysis-of-the-cdk2-functions-in-neuroblastoma
#1
Lijuan Bo, Bo Wei, Zhanfeng Wang, Daliang Kong, Zheng Gao, Zhuang Miao
The present study aimed to elucidate the potential mechanism of cyclin-dependent kinase 2 (CDK2) in neuroblastoma progression and to identify the candidate genes associated with neuroblastoma with CDK2 silencing. The microarray data of GSE16480 were obtained from the gene expression omnibus database. This dataset contained 15 samples: Neuroblastoma cell line IMR32 transfected with CDK2 shRNA at 0, 8, 24, 48 and 72 h (n=3 per group; total=15). Significant clusters associated with differentially expressed genes (DEGs) were identified using fuzzy C‑Means algorithm in the Mfuzz package...
December 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328377/feature-genes-in-metastatic-breast-cancer-identified-by-metade-and-svm-classifier-methods
#2
Youlin Tuo, Ning An, Ming Zhang
The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non‑metastasis samples were screened under the threshold of P<0.05. Based on the protein‑protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29316798/regulation-of-mitophagy-by-the-ubiquitin-pathway-in-neurodegenerative-diseases
#3
Shyamal Desai, Meredith Juncker, Catherine Kim
Mitophagy is a cellular process by which dysfunctional mitochondria are degraded via autophagy. Increasing empirical evidence proposes that this mitochondrial quality-control mechanism is defective in neurons of patients with various neurodegenerative diseases such as Ataxia Telangiectasia, Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis. Accumulation of defective mitochondria and the production of reactive oxygen species due to defective mitophagy have been identified as causes underlying neurodegenerative disease pathogenesis...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29316663/modulation-of-protein-quality-control-and-proteasome-to-autophagy-switch-in-immortalized-myoblasts-from-duchenne-muscular-dystrophy-patients
#4
Marion Wattin, Loïc Gaweda, Pascale Muller, Mathieu Baritaud, Charlotte Scholtes, Chloé Lozano, Kathrin Gieseler, Carole Kretz-Remy
The maintenance of proteome integrity is of primary importance in post-mitotic tissues such as muscle cells; thus, protein quality control mechanisms must be carefully regulated to ensure their optimal efficiency, a failure of these processes being associated with various muscular disorders. Duchenne muscular dystrophy (DMD) is one of the most common and severe forms of muscular dystrophies and is caused by mutations in the dystrophin gene. Protein quality control modulations have been diversely observed in degenerating muscles of patients suffering from DMD or in animal models of the disease...
January 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29295941/the-osfbk1-e3-ligase-subunit-affects-anther-and-root-secondary-cell-wall-thickenings-by-mediating-turn-over-of-a-cinnamoyl-coa-reductase
#5
Pratikshya Borah, Jitendra P Khurana
Regulated proteolysis by the Ubiquitin-26S proteasome system challenges transcription and phosphorylation in magnitude and is one of the most important regulatory mechanisms in plants. This article describes the characterization of a rice auxin-responsive Kelch-domain containing F-box protein, OsFBK1, found to be a component of an SCF E3 ligase by interaction studies in yeast. Rice transgenics of OsFBK1 displayed variations in anther and root secondary cell wall content; it could be corroborated by electron/confocal microscopy and lignification studies, with no apparent changes in auxin content/signalling pathway...
January 2, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29286091/identifying-heterogeneous-subtypes-of-gastric-cancer-and-subtype%C3%A2-specific-subpaths-of-microrna%C3%A2-target-pathways
#6
Yuanhang Li, Weijun Bai, Xu Zhang
The present study aimed to classify gastric cancer (GC) into subtypes and to screen the subtype‑specific genes, their targeted microRNAs (miRNAs) and enriched pathways to explore the putative mechanism of each GC subtypes. The GSE13861 data set was downloaded from the Gene Expression Omnibus and used to screen differential expression genes (DEGs) in GC samples based on the detection of imbalanced differential signal algorithm. The specific genes in each subtype were identified with the cut‑off criterion of U>0...
December 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29285618/oryza-sativa-salt-induced-ring-e3-ligase-2-ossirp2-acts-as-a-positive-regulator-of-transketolase-in-plant-response-to-salinity-and-osmotic-stress
#7
Sandeep Chapagain, Yong Chan Park, Ju Hee Kim, Cheol Seong Jang
A rice gene (OsSIRP2) encoding the RING Ub E3 ligase was highly induced under salinity stress and physically interacted with a transketolase (OsTKL1). Overexpression of OsSIRP2 conferred salinity and osmotic stress tolerance in plants. The RING E3 ligases play a vital role in post transitional modification through ubiquitination-mediated protein degradation that mediate plants responses during abiotic stresses and signal transduction. In this study, we report an Oryza sativa salt induced Really Interesting New Gene (RING) finger protein 2 gene (OsSIRP2) and elucidate its role under salinity and osmotic stress...
December 28, 2017: Planta
https://www.readbyqxmd.com/read/29279317/ak098656-a-novel-vascular-smooth-muscle-cell-dominant-long-noncoding-rna-promotes-hypertension
#8
Ling Jin, Xianjuan Lin, Lei Yang, Xiaofang Fan, Wenjie Wang, Shuangyue Li, Jing Li, Xiaoyan Liu, Minghui Bao, Xiao Cui, Jichun Yang, Qinghua Cui, Bin Geng, Jun Cai
Recent studies reported some long noncoding RNAs (lncRNAs)-mediated vascular smooth muscle cells (VSMCs) phenotypic switch, which was a common pathophysiological process of vascular diseases. However, whether human-specific expressed lncRNAs would modulate VSMCs phenotype and participate into the pathogenesis of essential hypertension remains unclear. By comparing the circulating lncRNAs expression profiles between hypertensive patients and healthy controls, we identified a lncRNA-AK098656, strongly upregulated in the plasma of hypertensive patients, and predominantly expressed in VSMCs...
February 2018: Hypertension
https://www.readbyqxmd.com/read/29274324/apoptosis-induction-and-inhibition-of-hela-cell-proliferation-by-alpha-naphthoflavone-and-resveratrol-are-aryl-hydrocarbon-receptor-independent
#9
Alegre Flores-Pérez, Guillermo Elizondo
Human papilloma viruses 16 and 18 express E6 and E7 oncoproteins. E6 activates and redirects E6-associated protein (E6AP), an E3 ubiquitin ligase. E6AP interacts with Ube2l3, an E2 ubiquitin conjugating enzyme protein (also known as UbcH7), to promote p53 ubiquitination and degradation by the 26S proteasome. Therefore, blocking E6-mediated p53 degradation might be an alternative treatment for cervical cancer. In addition, activation of the aryl hydrocarbon receptor (AHR) induces Ube2l3 expression, resulting in p53 ubiquitination and degradation...
December 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29273565/identification-of-d-amino-acid-oxidase-and-propiverine-interaction-partners-and-their-potential-role-in-the-propiverine-mediated-nephropathy
#10
Marcia Y Maier, Lisanne Luks, Oliver Baudendistel, Valentin Wittmann, Daniel R Dietrich
Propiverine, a frequently-prescribed pharmaceutical for the treatment of symptoms associated with overactive bladder syndrome, provoked massive intranuclear and cytosolic protein inclusions in rat proximal tubule epithelium, primarily consisting of the peroxisomal targeting signal 1 (PTS1) containing protein d-amino acid oxidase (DAAO). As this type of nephropathy was also observed for other drugs, the aim was to determine whether propiverine interferes with trafficking and/or import of peroxisomal proteins...
December 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29260397/the-microtubule-associated-ring-finger-protein-1-osmar1-acts-as-a-negative-regulator-for-salt-stress-response-through-the-regulation-of-ocpi2-o-sativa-chymotrypsin-protease-inhibitor-2
#11
Yong Chan Park, Sandeep Chapagain, Cheol Seong Jang
Our results suggest that a rice E3 ligase, OsMAR1, physically interacts with a cytosolic protein OCPI2 and may play an important role under salinity stress. Salt is an important abiotic stressor that negatively affects plant growth phases and alters development. Herein, we found that a rice gene, OsMAR1 (Oryza sativa microtubule-associated RING finger protein 1), encoding the RING E3 ligase was highly expressed in response to high salinity, water deficit, and ABA treatment. Fluorescence signals of its recombinant proteins were clearly associated with the microtubules in rice protoplasts...
December 19, 2017: Planta
https://www.readbyqxmd.com/read/29259103/the-b-box-domain-protein-bbx21-promotes-photomorphogenesis
#12
Dongqing Xu, Yan Jiang, Jian Li, Magnus Holm, Xing Wang Deng
B-box containing (BBX) proteins play critical roles in a variety of cellular and developmental processes in plants. BBX21 (also known as SALT TOLERANCE HOMOLOG 2), which contains two B-box domains in tandem at the N-terminus, has been previously demonstrated as a key component involved in the COP1-HY5 signaling hub. However, the exact molecular and physiological roles of B-box domains in BBX21 are largely unclear. Here, we found that structurally disruption of the second B-box domain, but not the first one, in BBX21 completely abolishes its biological and physiological activity in conferring hyper-photomorphogenetic phenotype in Arabidopsis...
December 19, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29251491/glycosylation-promotes-random-coil-to-helix-transition-in-a-region-of-a-protist-skp1-associated-with-f-box-binding
#13
Xianzhong Xu, Alexander Eletsky, M Osman Sheikh, James H Prestegard, Christopher M West
Cullin-Ring-Ligases mediate protein polyubiquitination, a signal for degradation in the 26S-proteasome. The CRL1 class consists of Skp1/cullin-1/F-box protein/Rbx1 (SCF) complexes that cyclically associate with ubiquitin-E2 to build the polyubiquitin chain. Within the SCF complex, the 162-amino acid DdSkp1 from Dictyostelium bridges cullin-1 with an F-box protein (FBP), the specificity factor for substrate selection. The hydroxylation-dependent glycosylation of Pro143 of DdSkp1 by a pentasaccharide forms the basis of a novel O2-sensing mechanism in the social amoeba Dictyostelium and other protists...
December 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/29249239/tools-to-investigate-the-ubiquitin-proteasome-system
#14
REVIEW
Yves Leestemaker, Huib Ovaa
Ubiquitin is a 76-amino acid regulatory protein involved in many important cellular processes. Ubiquitin can be attached to other proteins at either a lysine residue or to the N-terminus by the consecutive actions of E1, E2, and E3 enzymes. Ubiquitin can also be attached to itself, resulting in poly-ubiquitin chains. Ubiquitination affects substrate proteins in different ways, for example by resulting in degradation of the substrate protein by the 26S proteasome. Ubiquitination can be reversed by deubiquitinating enzymes, which either trim or remove ubiquitin chains from proteins...
December 2017: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/29237723/the-e3-ligase-drought-hypersensitive-negatively-regulates-cuticular-wax-biosynthesis-by-promoting-the-degradation-of-transcription-factor-roc4-in-rice
#15
Zhenyu Wang, Xiaojie Tian, Qingzhen Zhao, Zhiqi Liu, Xiufeng Li, Yuekun Ren, Jiaqi Tang, Jun Fang, Qijiang Xu, Qingyun Bu
Cuticular wax plays crucial roles in protecting plants from environmental stresses, particularly drought stress. Many enzyme-encoding genes and transcription factors involved in wax biosynthesis have been identified, but the underlying posttranslational regulatory mechanisms are poorly understood. Here, we demonstrate that DROUGHT HYPERSENSITIVE (DHS), encoding a Really Interesting New Gene (RING)-type protein, is a critical regulator of wax biosynthesis in rice (Oryza sativa). The cuticular wax contents were significantly reduced in DHS overexpression plants but increased in dhs mutants compared to the wild type, which resulted in a response opposite that of drought stress...
December 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/29233753/targeting-the-26s-proteasome-to-protect-against-proteotoxic-diseases
#16
REVIEW
Natura Myeku, Karen E Duff
Aggregates of misfolded proteins can compromise the function of the 26S proteasome complex, leaving neurons susceptible to accelerated and impaired protein homeostasis, thereby contributing to the pathogenesis of neurodegeneration. Strategies aimed at enhancing the function of the 26S proteasome via phosphorylation of key subunit epitopes have been effective in reducing protein aggregates in mouse models of disease. We discuss how phosphodiesterase (PDE) inhibitors and G protein-coupled receptor (GPCR)-targeted drugs might be considered as candidate therapeutics, acting on second messenger signal transduction...
December 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29232559/cilostazol-a-phosphodiesterase-3-inhibitor-activates-proteasome-proteolysis-and-attenuates-tauopathy-and-cognitive-decline
#17
Ari W Schaler, Natura Myeku
Alzheimer's disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29229809/proteasomes-tether-to-two-distinct-sites-at-the-nuclear-pore-complex
#18
Sahradha Albert, Miroslava Schaffer, Florian Beck, Shyamal Mosalaganti, Shoh Asano, Henry F Thomas, Jürgen M Plitzko, Martin Beck, Wolfgang Baumeister, Benjamin D Engel
The partitioning of cellular components between the nucleus and cytoplasm is the defining feature of eukaryotic life. The nuclear pore complex (NPC) selectively gates the transport of macromolecules between these compartments, but it is unknown whether surveillance mechanisms exist to reinforce this function. By leveraging in situ cryo-electron tomography to image the native cellular environment of Chlamydomonas reinhardtii, we observed that nuclear 26S proteasomes crowd around NPCs. Through a combination of subtomogram averaging and nanometer-precision localization, we identified two classes of proteasomes tethered via their Rpn9 subunits to two specific NPC locations: binding sites on the NPC basket that reflect its eightfold symmetry and more abundant binding sites at the inner nuclear membrane that encircle the NPC...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29217409/proteasome-phosphorylation-regulates-cocaine-induced-sensitization
#19
Frankie R Gonzales, Kristin K Howell, Lara E Dozier, Stephan G Anagnostaras, Gentry N Patrick
Repeated exposure to cocaine produces structural and functional modifications at synapses from neurons in several brain regions including the nucleus accumbens. These changes are thought to underlie cocaine-induced sensitization. The ubiquitin proteasome system plays a crucial role in the remodeling of synapses and has recently been implicated in addiction-related behavior. The ATPase Rpt6 subunit of the 26S proteasome is phosphorylated by Ca2+/calmodulin-dependent protein kinases II alpha at ser120 which is thought to regulate proteasome activity and distribution in neurons...
December 4, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29203562/impaired-protein-quality-control-during-left-ventricular-remodeling-in-mice-with-cardiac-restricted-overexpression-of-tumor-necrosis-factor
#20
Justin Hartupee, Gabor D Szalai, Wei Wang, Xiucui Ma, Abhinav Diwan, Douglas L Mann
BACKGROUND: Sustained inflammation in the heart is sufficient to provoke left ventricular dysfunction and left ventricular remodeling. Although inflammation has been linked to many of the biological changes responsible for adverse left ventricular remodeling, the relationship between inflammation and protein quality control in the heart is not well understood. METHODS AND RESULTS: To study the relationship between chronic inflammation and protein quality control, we used a mouse model of dilated cardiomyopathy driven by cardiac restricted overexpression of TNF (tumor necrosis factor; Myh6-sTNF)...
December 2017: Circulation. Heart Failure
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