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Ubiquitin

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https://www.readbyqxmd.com/read/28931206/metabolic-engineering-a-yeast-to-produce-astaxanthin
#1
Yu-Ju Lin, Jui-Jen Chang, Hao-Yeh Lin, Caroline Thia, Yi-Ying Kao, Chieh-Chen Huang, Wen-Hsiung Li
In this study, an astaxanthin-biosynthesis Kluyveromyces marxianus strain Sm23 was first constructed, which could produce 31µg/g DCW astaxanthin. Then, repeated genome integration of the key astaxanthin biosynthesis genes Hpchyb and bkt was done to increase gene copy number and astaxanthin yield. Four improved strains were obtained and the yield of astaxanthin and the total yield of carotenoids in a strain increased with the copy numbers of Hpchyb and bkt. To improve the yield further, the gene Hpchyb from Haematococcus pluvialis was modified by site-directed mutagenesis to increase the enzyme efficiency or/and to prevent the heterologous protein degradation by ubiquitination...
July 23, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28931009/ndfip-allows-nedd4-nedd4l-induced-aqp2-ubiquitination-and-degradation
#2
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
#3
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/28930533/53bp1-a-guardian-for-centrosomal-integrity
#4
Haeyoung Kim, Hyungshin Yim
53BP1 is known as a mediator in DNA damage response and a regulator of DNA double-stranded breaks (DSBs) repair. 53BP1 was recently reported to be a centrosomal protein and a binding partner of mitotic polo-like kinase 1 (Plk1). The stability of 53BP1, in response to DSBs, is regulated by its phosphorylation, deubiquitination, and ubiquitination. During mitosis, 53BP1 is stabilized by phosphorylation at S380, a putative binding region with polo-box domain of Plk1, and deubiquitination by ubiquitin-specific protease 7 (USP7)...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
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
#5
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
#6
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/28928904/depletion-of-the-third-complement-component-ameliorates-age-dependent-oxidative-stress-and-positively-modulates-autophagic-activity-in-aged-retinas-in-a-mouse-model
#7
Dorota Rogińska, Miłosz P Kawa, Ewa Pius-Sadowska, Renata Lejkowska, Karolina Łuczkowska, Barbara Wiszniewska, Kai Kaarniranta, Jussi J Paterno, Christian A Schmidt, Bogusław Machaliński, Anna Machalińska
The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT), electrophysiological function (ERG), and the expression of selected oxidative stress-, apoptosis-, and autophagy-related proteins were assessed in retinas of 12-month-old C3-deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1) alleviation of the age-dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2) significantly higher levels of antioxidant enzymes (catalase and glutathione reductase) and the antiapoptotic survivin and Mcl-1/Bak dimer, (3) lower expression of the cellular oxidative stress marker-4HNE-and decreased activity of proapoptotic caspase-3, (4) ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE) layer, and (5) significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28928851/%C3%AE-transducin-repeat-containing-e3-ubiquitin-protein-ligase-inhibits-migration-invasion-and-proliferation-of-glioma-cells
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28928220/characterization-of-a-cytoplasmic-glucosyltransferase-that-extends-the-core-trisaccharide-of-the-toxoplasma-skp1-e3-ubiquitin-ligase-subunit
#13
Kazi Rahman, Msano Mandalasi, Peng Zhao, M Osman Sheikh, Rahil Taujale, Hyun W Kim, Hanke van der Wel, Khushi Matta, Natarajan Kannan, John N Glushka, Lance Wells, Christopher M West
Skp1 is a subunit of the SCF (Skp1/Cullin-1/F-box protein) class of E3 ubiquitin ligases that are important for eukaryotic protein degradation. Unlike its animal counterparts, Skp1 from Toxoplasma gondii is hydroxylated by an O2-dependent prolyl-4-hydroxylase (PhyA), and the resulting hydroxyproline can subsequently be modified by a five-sugar chain. A similar modification is found in the social amoeba Dictyostelium, where it regulates SCF assembly and O2-dependent development. Homologous glycosyltransferases assemble a similar core trisaccharide in both organisms, and a bifunctional α-galactosyltransferase from CAZy family GT77 mediates addition of the final two sugars in Dictyostelium, generating Galα1,3Galα1,3Fucα1,2Galβ1,3GlcNAcα1-...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928219/o2-sensing-associated-glycosylation-exposes-the-f-box-combining-site-of-the-dictyostelium-skp1-subunit-in-e3-ubiquitin-ligases
#14
M Osman Sheikh, David Thieker, Gordon Chalmers, Christopher M Schafer, Mayumi Ishihara, Parastoo Azadi, Robert J Woods, John N Glushka, Brad Bendiak, James H Prestegard, Christopher M West
Skp1 is a conserved protein linking cullin-1 to F-box proteins in SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligases, which modify protein substrates with polyubiquitin chains that typically target them for 26S proteasome-mediated degradation. In Dictyostelium (a social amoeba), Toxoplasma gondii (the agent for human toxoplasmosis), and other protists, Skp1 is regulated by a unique pentasaccharide attached to hydroxylated Pro-143 within its C-terminal F-box binding domain. Prolyl hydroxylation of Skp1 contributes to O2-dependent Dictyostelium development, but full glycosylation at that position is required for optimal O2 sensing...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928040/p-3f-a-microtubule-polymerization-inhibitor-enhances-p53-stability-through-the-change-in-localization-of-rps27a
#15
Huai Wang, Jiang Feng, Tong Zhou, Lijun Wei, Jianming Zhou
Previously, we demonstrated that P-3F, a podophyllum derivative, exhibits a 297-fold enhancement in antitumor activity than VP-16, used as anticancer agent in clinical. The purpose of our present study was to investigate the precise antitumor mechanism action of P-3F. It showed that P-3F inhibited microtubule polymerization in a concentration-dependent manner. The results were in overall agreement with modeling and docking studies performed on P-3F and tubulin. In addition, P-3F increased the levels of P53, this in turn prolonged P53 half-life...
September 16, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28927521/when-the-guardian-sleeps-reactivation-of-the-p53-pathway-in-cancer
#16
REVIEW
Olaf Merkel, Ninon Taylor, Nicole Prutsch, Philipp B Staber, Richard Moriggl, Suzanne D Turner, Lukas Kenner
The p53 tumor suppressor is inactivated in most cancers, thus suggesting that loss of p53 is a prerequisite for tumor growth. Therefore, its reintroduction through different means bears great clinical potential. After a brief introduction to current knowledge of p53 and its regulation by the ubiquitin-ligases MDM2/MDMX and post-translational modifications, we will discuss small molecules that are able to reactivate specific, frequently observed mutant forms of p53 and their applicability for clinical purposes...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28927093/detailed-analysis-of-a-superficial-cd34-positive-fibroblastic-tumor-a-case-report-and-review-of-the-literature
#17
Kensaku Yamaga, Akihiro Fujita, Mari Osaki, Satoshi Kuwamoto, Naoko Ishiguro, Tadahito Yamamoto, Hideki Nagashima
Superficial cluster of differentiation (CD)34-positive fibroblastic tumor (SCPFT) is a rare mesenchymal neoplasm of borderline malignancy. It is characterized by a superficial location, marked cellular pleomorphism, an extremely low incidence of mitotic figures, and strong CD34 immunohistochemical positivity. As SCPFT is a recently described neoplasm, its characteristics are yet to be fully elucidated. To the best of our knowledge, no detailed studies regarding the imaging findings and cytogenetic analyses of SCPFTs exist...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927072/arsenic-trioxide-potentiates-sensitivity-of-multiple-myeloma-cells-to-lenalidomide-by-upregulating-cereblon-expression-levels
#18
Yuan Jian, Wen Gao, Chuanying Geng, Huixing Zhou, Yun Leng, Yanchen Li, Wenming Chen
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present study investigated how arsenic trioxide affected CRBN on MM cell lines and examined the anti-myeloma effect and mechanism in the combination of arsenic trioxide and lenalidomide...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926941/why-ubiquitin-has-not-evolved
#19
Douglas C Allan, James C Phillips
Ubiquitin, discovered less than 50 years ago, tags thousands of diseased proteins for destruction. It is small (only 76 amino acids), and is found unchanged in mammals, birds, fish, and even worms, indicating that ubiquitin is perfect. Key features of its functionality are identified here using critical point thermodynamic scaling theory. These include synchronized pivots and hinges, a stabilizing central pivot, and Fano interference between first- and second-order elements of correlated long-range (allosteric) globular surface shape transitions...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926063/methylglyoxal-attenuates-insulin-signaling-and-downregulates-the-enzymes-involved-in-cholesterol-biosynthesis
#20
Arati B Deshmukh, Shakuntala Bai, Aarthy T, Rubina S Kazi, Reema Banarjee, Rajeshwari Rathore, Vijayakumar Mv, Thulasiram Hv, Manoj Kumar Bhat, Kulkarni Mj
Methylglyoxal (MG) is a highly reactive dicarbonyl known to be elevated under the hyperglycemic conditions of diabetes and is implicated in the development of diabetic complications. Therefore, the current study investigates the role of MG in exacerbating insulin resistance at the insulin signaling level, as well as its effect on the global proteomic level. By using insulin sensitive rat muscle cells (L6) and Chinese hamster ovary (CHO) cells stably expressing the insulin receptor (IR) and a glucose transporter fused with green fluorescent protein (GLUT4-GFP), we have observed that MG impairs insulin signaling, inhibits GLUT4 translocation and reduces glucose uptake...
September 19, 2017: Molecular BioSystems
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