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https://www.readbyqxmd.com/read/29352658/role-of-hypoxia-inducible-factor-1-in-the-development-of-renal-fibrosis-in-mouse-obstructed-kidney-special-references-to-hif-1-dependent-gene-expression-of-profibrogenic-molecules
#1
Kazuya Kabei, Yu Tateishi, Masakazu Nozaki, Masako Tanaka, Masayuki Shiota, Mayuko Osada-Oka, Shunji Nishide, Junji Uchida, Tatsuya Nakatani, Shuhei Tomita, Katsuyuki Miura
The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO...
December 28, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29352268/cylindromatosis-mediates-neuronal-cell-death-in-vitro-and-in-vivo
#2
Goutham K Ganjam, Nicole Angela Terpolilli, Sebastian Diemert, Ina Eisenbach, Lena Hoffmann, Christina Reuther, Christiane Herden, Joachim Roth, Nikolaus Plesnila, Carsten Culmsee
The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#3
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352166/epstein-barr-virus-encoded-latent-membrane-protein-1-suppresses-necroptosis-through-targeting-ripk1-3-ubiquitination
#4
Xiaolan Liu, Yueshuo Li, Songling Peng, Xinfang Yu, Wei Li, Feng Shi, Xiangjian Luo, Min Tang, Zheqiong Tan, A M Bode, Ya Cao
Necroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352077/whole-genome-sequencing-of-suppressor-dna-mixtures-identifies-pathways-that-compensate-for-chromosome-segregation-defects-in-schizosaccharomyces-pombe
#5
Xingya Xu, Li Wang, Mitsuhiro Yanagida
Suppressor screening is a powerful method to identify genes that when mutated, rescue the temperature sensitivity of the original mutation. Previously, however, identification of suppressor mutations has been technically difficult. Due to the small genome size of Schizosaccharomyces pombe, we developed a spontaneous suppressor screening technique, followed by a cost-effective sequencing method. Genomic DNAs of 10 revertants which survived at the restrictive temperature of the original temperature sensitive (ts) mutant were mixed together as one sample before constructing a library for sequencing...
January 19, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29351997/spatiotemporal-organization-of-exocytosis-emerges-during-neuronal-shape-change
#6
Fabio L Urbina, Shawn M Gomez, Stephanie L Gupton
Neurite elongation and branching in developing neurons requires plasmalemma expansion, hypothesized to occur primarily via exocytosis. We posited that exocytosis in developing neurons and nonneuronal cells would exhibit distinct spatiotemporal organization. We exploited total internal reflection fluorescence microscopy to image vesicle-associated membrane protein (VAMP)-pHluorin-mediated exocytosis in mouse embryonic cortical neurons and interphase melanoma cells, and developed computer-vision software and statistical tools to uncover spatiotemporal aspects of exocytosis...
January 19, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29351849/the-dfm1-derlin-is-required-for-erad-retrotranslocation-of-integral-membrane-proteins
#7
Sonya Neal, Philipp A Jaeger, Sascha H Duttke, Christopher K Benner, Christopher Glass, Trey Ideker, Randolph Hampton
Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway. Retrotranslocation of ubiquitinated substrates to the cytosol is a universal feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes normal retrotranslocation independently of known ERAD factors, and the new SPOCK (single plate orf compendium kit) micro-library to query all yeast genes, we found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD and DOA ERAD pathway integral membrane substrates...
January 18, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29351798/comparative-salivary-proteomics-analysis-of-children-with-and-without-dental-caries-using-the-itraq-mrm-approach
#8
Kun Wang, Yufei Wang, Xiuqing Wang, Qian Ren, Sili Han, Longjiang Ding, Zhongcheng Li, Xuedong Zhou, Wei Li, Linglin Zhang
BACKGROUND: Dental caries is a major worldwide oral disease afflicting a large proportion of children. As an important host factor of caries susceptibility, saliva plays a significant role in the occurrence and development of caries. The aim of the present study was to characterize the healthy and cariogenic salivary proteome and determine the changes in salivary protein expression of children with varying degrees of active caries, also to establish salivary proteome profiles with a potential therapeutic use against dental caries...
January 19, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29351515/understanding-key-mechanisms-of-exercise-induced-cardiac-protection-to-mitigate-disease-current-knowledge-and-emerging-concepts
#9
Bianca C Bernardo, Jenny Y Y Ooi, Kate L Weeks, Natalie L Patterson, Julie R McMullen
The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351241/molecular-characterization-and-expression-profiles-of-sp-uchl3-and-sp-uchl5-during-gonad-development-of-scylla-paramamosain
#10
Kunhuang Han, Yanbin Dai, Ziping Zhang, Zhihua Zou, Yilei Wang
Ubiquitin C-terminal hydrolases (UCHLs) are a subset of deubiquitinating enzymes, and are involved in numerous physiological processes. However, the role of UCHLs during gonad development has not been studied in crustaceans. In this study, we have first cloned and analyzed expression profiling of Sp-uchl3 and Sp-uchl5 genes from mud crab Scylla paramamosain. The full-length cDNA of Sp-uchl3 is of 1804 bp. Its expression level in the ovary was significantly higher than in other tissues (p < 0.01), and during gonadal development, its expression in both O1 and O5 stages was significantly higher than in the other three stages of ovaries (p < 0...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29350614/lipg-signaling-promotes-tumor-initiation-and-metastasis-of-human-basal-like-triple-negative-breast-cancer
#11
Pang-Kuo Lo, Yuan Yao, Ji Shin Lee, Yongshu Zhang, Weiliang Huang, Maureen A Kane, Qun Zhou
Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29349575/parkin-in-parkinson-s-disease-and-cancer-a-double-edged-sword
#12
REVIEW
Khushnuma Wahabi, Ahmad Perwez, Moshahid A Rizvi
Parkin for more than a decade has been portrayed as a neuroprotector gene is now increasingly emerging as a multifaceted gene that can exert entirely opposite effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a neurological disease, progresses due to excess in cell death, while, in case of cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor gene, involved in a variety of cancers...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29348847/distinct-roles-of-traf6-and-tak1-in-the-regulation-of-adipocyte-survival-thermogenesis-program-and-high-fat-diet-induced-obesity
#13
Yann S Gallot, Joseph D McMillan, Guangyan Xiong, Kyle R Bohnert, Alex R Straughn, Bradford G Hill, Ashok Kumar
Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance are common features of obesity and a risk factor for cancer. Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also possesses a non-conventional E3 ubiquitin ligase activity. In response to receptor-mediated events, TRAF6 activates transforming growth factor-activated kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B (NF-κB) signaling pathways. However, the roles of TRAF6 and TAK1 in the regulation of adipocyte function remain less understood...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348603/comprehensive-list-of-sumo-targets-in-caenorhabditis-elegans-and-its-implication-for-evolutionary-conservation-of-sumo-signaling
#14
Krzysztof Drabikowski, Jacqueline Ferralli, Michal Kistowski, Jacek Oledzki, Michal Dadlez, Ruth Chiquet-Ehrismann
Post-translational modification by small ubiquitin-related modifier (SUMO) is a key regulator of cell physiology, modulating protein-protein and protein-DNA interactions. Recently, SUMO modifications were postulated to be involved in response to various stress stimuli. We aimed to identify the near complete set of proteins modified by SUMO and the dynamics of the modification in stress conditions in the higher eukaryote, Caenorhabditis elegans. We identified 874 proteins modified by SUMO in the worm. We have analyzed the SUMO modification in stress conditions including heat shock, DNA damage, arsenite induced cellular stress, ER and osmotic stress...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348145/fbxl13-directs-the-proteolysis-of-cep192-to-regulate-centrosome-homeostasis-and-cell-migration
#15
Ella Fung, Carmen Richter, Hong-Bin Yang, Isabell Schäffer, Roman Fischer, Benedikt M Kessler, Florian Bassermann, Vincenzo D'Angiolella
Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192...
January 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29346421/the-absence-of-specific-yeast-heat-shock-proteins-leads-to-abnormal-aggregation-and-compromised-autophagic-clearance-of-mutant-huntingtin-proteins
#16
Ryan Higgins, Marie-Helene Kabbaj, Alexa Hatcher, Yanchang Wang
The functionality of a protein depends on its correct folding, but newly synthesized proteins are susceptible to aberrant folding and aggregation. Heat shock proteins (HSPs) function as molecular chaperones that aid in protein folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat expansion in the Huntingtin gene (HTT) results in the expression of misfolded Huntingtin protein (Htt), which contributes to the development of Huntington's disease. We previously found that the degradation of mutated Htt with polyQ expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy...
2018: PloS One
https://www.readbyqxmd.com/read/29346416/decoding-the-network-of-trypanosoma-brucei-proteins-that-determines-sensitivity-to-apolipoprotein-l1
#17
Rachel B Currier, Anneli Cooper, Hollie Burrell-Saward, Annette MacLeod, Sam Alsford
In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein-L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non-infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been extensively characterised, our understanding of the range of factors that drive apoL1 action in T. b. brucei is limited...
January 18, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29345925/catalytic-mechanism-of-the-ubiquitin-like-nedd8-transfer-in-ring-e3-e2-nedd8-target-complex-from-qm-mm-free-energy-simulations
#18
Yufei Yue, Yue Ma, Ping Qian, Hong Guo
Ubiquitin-like (UBL) protein modifications play a key role in regulating protein function. In contrast to the ubiquitin (UB) and small ubiquitin-like modifier (SUMO) which are ligated to a massive segment of proteome, the UBL NEDD8 is highly selective for modifying a lysine residue on closely related cullin proteins (CULs). In this study, the X-ray structure of a trapped E3-E2~NEDD8-target intermediate (RBX1-UBC1~NEDD8-CUL1-DCN1) is used to build computer models, and combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) and free energy (potential of mean force) simulations are performed to investigate the catalytic mechanism of the NEDD8 transfer from E2 to the lysine residue (K720) on the substrate in the complex...
January 18, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29345285/the-epitranscriptome-m6a-writer-mettl3-promotes-chemo-and-radioresistance-in-pancreatic-cancer-cells
#19
Kosuke Taketo, Masamitsu Konno, Ayumu Asai, Jun Koseki, Masayasu Toratani, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii, Kazuhiko Ogawa
N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in mammalian mRNA. Recent years have seen substantial progress in m6A epitranscriptomics, indicating its crucial roles in the initiation and progression of cancer through regulation of RNA stabilities, mRNA splicing, microRNA processing and mRNA translation. However, by what means m6A is dynamically regulated or written by enzymatic components represented by methyltransferase-like 3 (METTL3) and how m6A is significant for each of the numerous genes remain unclear...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344651/identification-of-genes-and-pathways-in-the-synovia-of-women-with-osteoarthritis-by-bioinformatics-analysis
#20
Bobin Mi, Guohui Liu, Wu Zhou, Huijuan Lv, Yi Liu, Jing Liu
Osteoarthritis (OA) has a high prevalence in female patients and sex may be a key factor affecting the progression of OA. The aim of the present study was to identify genetic signatures in the synovial membranes of female patients with OA and to elucidate the potential associated molecular mechanisms. The gene expression profiles of the GSE55457 and GSE55584 datasets were obtained from the Gene Expression Omnibus database. Data of two synovial membranes from normal female individuals (GSM1337306 and GSM1337310) and two synovial membranes from female patients affected by OA (GSM1337327 and GSM1337330) were obtained from the dataset GSE55457, and those of three synovial membranes from female patients affected by OA (GSM1339628, GSM1339629 and GSM1339632) were obtained from the dataset GSE55584...
January 15, 2018: Molecular Medicine Reports
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