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https://www.readbyqxmd.com/read/28938631/microrna-455-targets-cullin-3-to-activate-nrf2-signaling-and-protect-human-osteoblasts-from-hydrogen-peroxide
#1
Dawei Xu, Hao Zhu, Chengniu Wang, Xinhui Zhu, Genxiang Liu, Chu Chen, Zhiming Cui
Over-production of hydrogen peroxide (H2O2) will lead to human osteoblast dysfunction and apoptosis, causing progression of osteoporosis and osteonecrosis. NF-E2-related factor 2 (Nrf2) is a well-characterized anti-oxidant signaling. Cullin 3 (Cul3) ubiquitin E3 ligase dictates Nrf2 degradation. We demonstrate that microRNA-455 ("miR-455") is a putative Cul3-targeting microRNA. Forced-expression of miR-455 in both hFOB1. 19 osteoblast cell line and primary human osteoblasts induced Cul3 degradation and Nrf2 protein stabilization, which led to subsequent transcription of ARE (anti-oxidant response element)-dependent genes (NQO1, HO1 and GCLC)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938460/huwe1-regulates-the-establishment-and-maintenance-of-spermatogonia-by-suppressing-dna-damage-response
#2
Kin Lam Fok, Rohini Bose, Kai Sheng, Ching-Wen Chang, Mira Katz-Egorov, Martine Culty, Sicheng Su, Ming Yang, Ye Chun Ruan, Hsiao-Chang Chan, Antonio Iavarone, Anna Lasorella, Regina Cencic, Jerry Pelletier, Makoto Nagano, Wenming Xu, Simon S Wing
Spermatogenesis is sustained by a heterogeneous population of spermatogonia which includes the spermatogonial stem cells. However, the mechanisms underlying their establishment from gonocyte embryonic precursors and their maintenance thereafter remain largely unknown. Here, we report that inactivation of the ubiquitin ligase Huwe1 in male germ cells in mice led to the degeneration of spermatogonia in neonates and resulted in a Sertoli cell-only phenotype in the adult. Huwe1 KO gonocytes showed a decrease in mitotic re-entry which inhibited their transition to spermatogonia...
August 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938065/in-vitro-selection-of-diversely-functionalized-aptamers
#3
Dehui Kong, Wayland Yeung, Ryan Hili
We describe the application of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the evolution of a diversely functionalized nucleic acid aptamer for human α-thrombin. Using a 256-membered ANNNN co-monomer library comprising 16 sub-libraries modi-fied with different functional groups, a highly-functionalized aptamer for thrombin was raised with a dissociation constant of 1.6 nM. The aptamer was found to be selective for thrombin, and re-quired the modifications for binding affinity...
September 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28937247/amino-acid-concentrations-and-protein-metabolism-of-two-types-of-rat-skeletal-muscle-in-postprandial-state-and-after-brief-starvation
#4
M Holeček, S Mičuda
We have investigated amino acid concentrations and protein metabolism in musculus extensor digitorum longus (EDL, fast-twitch, white muscle) and musculus soleus (SOL, slow-twitch, red muscle) of rats sacrificed in the fed state or after one day of starvation. Fractional protein synthesis rates (FRPS) were measured using the flooding dose method (L-[3,4,5-3H]phenylalanine). Activities of two major proteolytic systems in muscle (the ubiquitin-proteasome and lysosomal) were examined by measurement of chymotrypsin like activity of proteasome (CTLA), expression of ubiquitin ligases atrogin-1 and muscle-ring-finger-1 (MuRF-1), and cathepsin B and L activities...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28934494/derivatives-of-bst-like-gss-polymerase-with-improved-processivity-and-inhibitor-tolerance
#5
Igor P Oscorbin, Ekaterina A Belousova, Ulyana A Boyarskikh, Aleksandr I Zakabunin, Evgeny A Khrapov, Maksim L Filipenko
At the moment, one of the actual trends in medical diagnostics is a development of methods for practical applications such as point-of-care testing, POCT or research tools, for example, whole genome amplification, WGA. All the techniques are based on using of specific DNA polymerases having strand displacement activity, high synthetic processivity, fidelity and, most significantly, tolerance to contaminants, appearing from analysed biological samples or collected under purification procedures. Here, we have designed a set of fusion enzymes based on catalytic domain of DNA polymerase I from Geobacillus sp...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#6
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28933980/panduratin-a-prevents-tumor-necrosis-factor-alpha-induced-muscle-atrophy-in-l6-rat-skeletal-muscle-cells
#7
Bo-Kyung Sa, Changhee Kim, Mi-Bo Kim, Jae-Kwan Hwang
Panduratin A, a prenylated chalcone compound, has anti-obesity, anti-bacterial, anti-cancer, anti-inflammatory, and anti-oxidative activities. However, its preventive effect on muscle atrophy has not been studied. The purpose of this study was to evaluate the inhibitory effect of panduratin A on muscle atrophy and to investigate its molecular mechanisms in tumor necrosis factor-alpha (TNF-α)-treated L6 rat skeletal muscle cells. Panduratin A restored the myotube diameter reduced by TNF-α. At the molecular level, panduratin A elevated phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin pathway and stimulated the MyoD and myogenin mRNA expression decreased by TNF-α...
September 21, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28932723/anaphase-promoting-complex-7-is-a-prognostic-factor-in-human-colorectal-cancer
#8
Ik Yong Kim, Hye Yeon Kwon, Kwang Hwa Park, Dae Sung Kim
PURPOSE: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity and is required for ubiquitination of securin and cyclin-B. Several APC-targeting molecules are reported to be oncogenes. Dysregulation of APC may be associated with tumorigenesis. This study examines the relationship between APC expression and clinicopathological factors and evaluates the possibility of an aberrant APC function in colorectal carcinomas (CRCs). METHODS: To determine whether the loss of APC7 expression is related to tumorigenesis, we used tissue micro-arrays in 114 resected CRCs to scrutinize the expressions of APC7 and Ki-67 immunohistochemistry and to find relations with clinocopathologic parameters...
August 2017: Annals of Coloproctology
https://www.readbyqxmd.com/read/28932620/distinct-roles-of-catalytic-cysteine-and-histidine-in-the-protease-and-ligase-mechanisms-of-human-legumain-as-revealed-by-dft-based-qm-mm-simulations
#9
Brigitta Elsässer, Florian B Zauner, Johann Messner, Wai Tuck Soh, Elfriede Dall, Hans Brandstetter
The cysteine protease enzyme legumain hydrolyzes peptide bonds with high specificity after asparagine and under more acidic conditions after aspartic acid [Baker E. N.J. Mol. Biol.1980, 141, 441-484; Baker E. N.; J. Mol. Biol.1977, 111, 207-210; Drenth J.; Biochemistry1976, 15, 3731-3738; Menard R.; J. Cell. Biochem.1994, 137; Polgar L.Eur. J. Biochem.1978, 88, 513-521; Storer A. C.; Methods Enzymol.1994, 244, 486-500. Remarkably, legumain additionally exhibits ligase activity that prevails at pH > 5.5. The atomic reaction mechanisms including their pH dependence are only partly understood...
September 1, 2017: ACS Catalysis
https://www.readbyqxmd.com/read/28931592/ubiquitin-ligase-spsb4-diminishes-cell-repulsive-responses-mediated-by-ephb2
#10
Fumihiko Okumura, Akiko Joo-Okumura, Keisuke Obara, Alexander Petersen, Akihiko Nishikimi, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura
Eph receptor tyrosine kinases and their ephrin ligands are overexpressed in various human cancers, including colorectal malignancies, suggesting important roles in many aspects of cancer development and progression as well as in cellular repulsive responses. The ectodomain of EphB2 receptor is cleaved by metalloproteinases (MMPs) MMP-2/MMP-9 and released into the extracellular space after stimulation by its ligand. The remaining membrane-associated fragment is further cleaved by the presenilin-dependent γ-secretase and releases an intracellular peptide that has tyrosine kinase activity...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28931009/ndfip-allows-nedd4-nedd4l-induced-aqp2-ubiquitination-and-degradation
#11
Christiane Trimpert, Daniel Wesche, Theun de Groot, Martha M Pimentel Rodriguez, Victoria Wong, Dennis T M van den Berg, Lydie Cheval, Carolina A Ariza, Alain Doucet, Igor Stagljar, Peter M T Deen
Regulation of our water homeostasis is fine-tuned by dynamic translocation of Aquaporin-2 (AQP2)-bearing vesicles to and from the plasma membrane of renal principal cells. Whereas binding of vasopressin to its type-2 receptor initiates a cAMP-protein kinase A cascade and AQP2 translocation to the apical membrane, this is counteracted by protein kinase C-activating hormones, resulting in ubiquitination-dependent internalization of AQP2. The proteins targeting AQP2 for ubiquitin-mediated degradation are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28930681/parkin-independent-mitophagy-controls-chemotherapeutic-response-in-cancer-cells
#12
Elodie Villa, Emma Proïcs, Camila Rubio-Patiño, Sandrine Obba, Barbara Zunino, Jozef P Bossowski, Romain M Rozier, Johanna Chiche, Laura Mondragón, Joel S Riley, Sandrine Marchetti, Els Verhoeyen, Stephen W G Tait, Jean-Ehrland Ricci
Mitophagy is an evolutionarily conserved process that selectively targets impaired mitochondria for degradation. Defects in mitophagy are often associated with diverse pathologies, including cancer. Because the main known regulators of mitophagy are frequently inactivated in cancer cells, the mechanisms that regulate mitophagy in cancer cells are not fully understood. Here, we identified an E3 ubiquitin ligase (ARIH1/HHARI) that triggers mitophagy in cancer cells in a PINK1-dependent manner. We found that ARIH1/HHARI polyubiquitinates damaged mitochondria, leading to their removal via autophagy...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930678/dna-ligase-iv-guides-end-processing-choice-during-nonhomologous-end-joining
#13
Michael P Conlin, Dylan A Reid, George W Small, Howard H Chang, Go Watanabe, Michael R Lieber, Dale A Ramsden, Eli Rothenberg
Nonhomologous end joining (NHEJ) must adapt to diverse end structures during repair of chromosome breaks. Here, we investigate the mechanistic basis for this flexibility. DNA ends are aligned in a paired-end complex (PEC) by Ku, XLF, XRCC4, and DNA ligase IV (LIG4); we show by single-molecule analysis how terminal mispairs lead to mobilization of ends within PECs and consequent sampling of more end-alignment configurations. This remodeling is essential for direct ligation of damaged and mispaired ends during cellular NHEJ, since remodeling and ligation of such ends both require a LIG4-specific structural motif, insert1...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930190/oligonol-a-low-molecular-weight-polyphenol-derived-from-lychee-alleviates-muscle-loss-in-diabetes-by-suppressing-atrogin-1-and-murf1
#14
Hung-Wen Liu, Yen-Ju Chen, Yun-Ching Chang, Sue-Joan Chang
Stimulation of the ubiquitin-proteasome pathway-especially E3 ubiquitin ligases Atrogin-1 and MuRF1-is associated with muscle loss in diabetes. Elevated lipid metabolites impair myogenesis. Oligonol, a low molecular weight polyphenol derived from lychee, exhibited anti-diabetic and anti-obesity properties, suggesting it could be a proper supplement for attenuating muscle loss. Dietary (10 weeks) oligonol supplementation (20 or 200 mg/kg diet) on the skeletal muscle loss was investigated in diabetic db/db mice...
September 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28929193/immune-regulation-by-ubiquitin-tagging-as-checkpoint-code
#15
Peng Zeng, Jieyu Ma, Runqing Yang, Yun-Cai Liu
The immune system is equipped with effective machinery to mobilize its activation to defend invading microorganisms, and at the same time, to refrain from attacking its own tissues to maintain immune tolerance. The balance of activation and tolerance is tightly controlled by diverse mechanisms, since breakdown of tolerance could result in disastrous consequences such as the development of autoimmune diseases. One of the mechanisms is by the means of protein ubiquitination, which involves the process of tagging a small peptide ubiquitin to protein substrates...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28928851/%C3%AE-transducin-repeat-containing-e3-ubiquitin-protein-ligase-inhibits-migration-invasion-and-proliferation-of-glioma-cells
#16
Jun Liang, Wei-Feng Wang, Shao Xie, Xian-Li Zhang, Wei-Feng Qi, Xiu-Ping Zhou, Jin-Xia Hu, Qiong Shi, Ru-Tong Yu
β-transducin repeat-containing E3 ubiquitin protein ligase (β-TrCP) serves as the substrate recognition subunit for the Skp1-Cullin1-F-box protein E3 ubiquitin ligase, which recognizes the double phosphorylated DSG (X)2+nS destruction motif in various substrates that are essential for numerous aspects of tumorigenesis and regulates several important signaling pathways. However, the biological significance of β-TrCP in glioma progression remains largely unknown. A previous study by the authors demonstrated that the levels of β-TrCP protein expression in brain glioma tissues were significantly lower compared with non-tumorous tissues and that higher grades of gliomas exhibited lower levels of β-TrCP expression in comparison with lower glioma grades...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928831/park2-negatively-regulates-the-metastasis-and-epithelial-mesenchymal-transition-of-glioblastoma-cells-via-zeb1
#17
Haiyang Wang, Zhenfeng Jiang, Meng Na, Haitao Ge, Chongyang Tang, Hong Shen, Zhiguo Lin
Glioblastoma multiforme (GBM), one of the most aggressive human malignant brain tumors, is induced by multiple complex pathological mechanisms. The main cause of mortality in patients with GBM is the invasion-metastasis cascade of tumor cells. The dysfunction of Parkinson protein 2 E3 ubiquitin protein ligase (PARK2) is closely linked with the development of certain human cancers. However, whether PARK2 is associated with metastasis in GBM remains unknown. The present study demonstrated that the metastasis and invasion of U87 cells were significantly repressed by PARK2 overexpression...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928809/nedd4-promotes-cell-growth-and-migration-via-pten-pi3k-akt-signaling-in-hepatocellular-carcinoma
#18
Zhi-Jun Huang, Jun-Jun Zhu, Xiao-Yu Yang, Ewelina Biskup
The novel E3 ubiquitin-protein ligase neural precursor cell-expressed developmentally downregulated protein 4 (NEDD4) has been implicated as a crucial factor promoting the tumorigenesis of several types of cancer. The present study investigated the oncogenic role of NEDD4 in hepatocellular carcinoma (HCC) by targeted small interfering RNA silencing of the tumor suppressor phosphatase and tensin homolog (PTEN). Using normal hepatocyte and HCC cell lines, the influence of NEDD4 depletion on proliferation and migration as well as on the PTEN/phosphatidylinositol-3-kinase/protein kinase B signaling pathway was assessed...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928488/ubiquitylation-at-the-crossroads-of-development-and-disease
#19
REVIEW
Michael Rape
Human development requires intricate cell specification and communication pathways that allow an embryo to generate and appropriately connect more than 200 different cell types. Key to the successful completion of this differentiation programme is the quantitative and reversible regulation of core signalling networks, and post-translational modification with ubiquitin provides embryos with an essential tool to accomplish this task. Instigated by E3 ligases and reversed by deubiquitylases, ubiquitylation controls many processes that are fundamental for development, such as cell division, fate specification and migration...
September 20, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28928274/the-ubiquitin-ligase-e3-psh1p-is-required-for-proper-segregation-of-both-centromeric-and-two-micron-plasmids-in-saccharomyces-cerevisiae
#20
Meredith B Metzger, Jessica L Scales, Mitchell F Dunklebarger, Allan M Weissman
Protein degradation by the ubiquitin-proteasome system is essential to many processes. We sought to assess its involvement in the turnover of mitochondrial proteins in Saccharomyces cerevisiae We find that deletion of a specific ubiquitin ligase (E3), Psh1p, increases the abundance of a temperature-sensitive mitochondrial protein, mia40-4pHA, when it is expressed from a centromeric plasmid. Deletion of Psh1p unexpectedly elevates the levels of other proteins expressed from centromeric plasmids. Loss of Psh1p does not increase the rate of turn-over of mia40-4pHA, affect total protein synthesis, or increase the protein levels of chromosomal genes...
September 19, 2017: G3: Genes—Genomes—Genetics
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