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Ubiquitin

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https://www.readbyqxmd.com/read/29782878/the-ubiquitin-protein-ligase-e6ap-ube3a-supports-early-encephalomyocarditis-virus-replication
#1
Marybeth Carmody, Joshua T Zimmer, Camille H Cushman, Thao Nguyen, T Glen Lawson
Many viruses make use of, and even direct, the ubiquitin-proteasome system to facilitate the generation of a cellular environment favorable for virus replication, while host cells use selected protein ubiquitylation pathways for antiviral defense. Relatively little information has been acquired, however, regarding the extent to which protein ubiquitylation determines the replication success of picornaviruses. Here we report that the ubiquitin-protein ligase E6AP/UBE3A, recently shown to be a participant in encephalomyocarditis virus (EMCV) 3C protease concentration regulation, also facilitates the early stages of EMCV replication, probably by a mechanism that does not involve 3C protease ubiquitylation...
May 18, 2018: Virus Research
https://www.readbyqxmd.com/read/29782494/ubiquitin-dependent-proteolysis-of-cxcl7-leads-to-posterior-longitudinal-ligament-ossification
#2
Michiyo Tsuru, Atsushi Ono, Hideaki Umeyama, Masahiro Takeuchi, Kensei Nagata
Ossification of the posterior longitudinal ligament (OPLL), a spinal ligament, reduces the range of motion in limbs. No treatment is currently available for OPLL, which is why therapies are urgently needed. OPLL occurs in obesity, is more common in men, and has an onset after 40 years of age. The mechanisms underlying OPLL remain unclear. In this study, we performed a serum proteomic analysis in both OPLL patients and healthy subjects to identify factors potentially involved in the development of OPLL, and found reduced levels of a protein that might underlie the pathology of OPLL...
2018: PloS One
https://www.readbyqxmd.com/read/29781103/targeting-ubiquitin-specific-protease-7-in-cancer-a-deubiquitinase-with-great-prospects
#3
REVIEW
Farjana Yeasmin Khusbu, Fang-Zhi Chen, Han-Chun Chen
Deubiquitinase (DUB)-mediated cleavage of ubiquitin chain balances ubiquitination and deubiquitination for determining protein fate. USP7 is one of the best characterized DUBs and functionally important. Numerous proteins have been identified as potential substrates and binding partners of USP7; those play crucial roles in diverse array of cellular and biological processes including tumour suppression, cell cycle, DNA repair, chromatin remodelling, and epigenetic regulation. This review aims at summarizing the current knowledge of this wide association of USP7 with many cellular processes that enlightens the possibility of abnormal USP7 activity in promoting oncogenesis and the importance of identification of specific inhibitors...
May 20, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29780898/sumoylation-and-phosphorylation-cross-talk-in-hepatocellular-carcinoma
#4
REVIEW
Maria Lauda Tomasi, Komal Ramani
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. The large spectrum of protein post-translational modification (PTM) includes numerous critical signaling events that occur during neoplastic transformation. PTMs occur to nearly all proteins and increase the functional diversity of proteins. We have reviewed the role of two major PTMs, SUMOylation and phosphorylation, in the altered signaling of key players in HCC...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29779948/the-eukaryotic-proteome-is-shaped-by-e3-ubiquitin-ligases-targeting-c-terminal-degrons
#5
Itay Koren, Richard T Timms, Tomasz Kula, Qikai Xu, Mamie Z Li, Stephen J Elledge
Degrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small, and a facile technology to characterize them is lacking. Using a strategy combining global protein stability (GPS) profiling with a synthetic human peptidome, we identify thousands of peptides containing degron activity. Employing CRISPR screening, we establish that the stability of many proteins is regulated through degrons located at their C terminus...
May 11, 2018: Cell
https://www.readbyqxmd.com/read/29779941/the-epigenetic-state-of-prdm16-regulated-enhancers-in-radial-glia-controls-cortical-neuron-position
#6
José-Manuel Baizabal, Meeta Mistry, Miguel Turrero García, Nicolás Gómez, Olubusola Olukoya, Diana Tran, Matthew B Johnson, Christopher A Walsh, Corey C Harwell
The epigenetic landscape is dynamically remodeled during neurogenesis. However, it is not understood how chromatin modifications in neural stem cells instruct the formation of complex structures in the brain. We report that the histone methyltransferase PRDM16 is required in radial glia to regulate lineage-autonomous and stage-specific gene expression programs that control number and position of upper layer cortical projection neurons. PRDM16 regulates the epigenetic state of transcriptional enhancers to activate genes involved in intermediate progenitor cell production and repress genes involved in cell migration...
May 15, 2018: Neuron
https://www.readbyqxmd.com/read/29779101/the-role-of-epibionts-of-bacteria-of-the-genus-pseudoalteromonas-and-cellular-proteasomes-in-the-adaptive-plasticity-of-marine-cold-water-sponges
#7
O I Kravchuk, A I Lavrov, A D Finoshin, N G Gornostaev, A A Georgiev, S B Abaturova, V S Mikhailov, Yu V Lyupina
It was found that cells of different color morphs of the cold-water marine sponges Halichondria panicea (Pallas, 1766) of the class Demospongiae differ in the content of epibionts of bacteria of the genus Pseudoalteromonas. The sponge cells with elevated levels of epibionts of bacteria of the genus Pseudoalteromonas showed an increased expression of Hsp70 proteins but had a reduced level of the proteasomal catalytic beta 5 subunit, which was accompanied by a change in their activity. Probably, epibionts of bacteria of the genus Pseudoalteromonas may affect the ubiquitin-proteasome system in the cells of cold-water marine sponges and, thereby, ensure their adaptive plasticity...
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29778604/structural-basis-for-the-interaction-of-mutasome-assembly-factor-rev1-with-ubiquitin
#8
Gaofeng Cui, Maria Victoria Botuyan, Georges Mer
REV1 is an evolutionarily conserved Translesion synthesis (TLS) DNA polymerase and an assembly factor key for the recruitment of other TLS polymerases to DNA damage sites. REV1-mediated recognition of ubiquitin in the proliferative cell nuclear antigen (PCNA) is thought to be the trigger for TLS activation. Here we report the solution nuclear magnetic resonance (NMR) structure of a 108-residue fragment of human REV1 encompassing the two putative ubiquitin-binding motifs UBM1 and UBM2 in complex with ubiquitin...
May 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29777907/novel-snps-of-wnk1-and-akr1c3-are-associated-with-preeclampsia
#9
Cheng-Juan Sun, Lin Li, Xueyan Li, Wei-Yuan Zhang, Xiao-Wei Liu
Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (β2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777785/psmd2-regulates-breast-cancer-cell-proliferation-and-cell-cycle-progression-by-modulating-p21-and-p27-proteasomal-degradation
#10
Yunhai Li, Jing Huang, Beilei Zeng, Dejuan Yang, Jiazheng Sun, Xuedong Yin, Mengqi Lu, Zhu Qiu, Weiyan Peng, Tingxiu Xiang, Hongzhong Li, Guosheng Ren
Alterations in the ubiquitin-proteasome system (UPS) and UPS-associated proteins have been implicated in the development of many human malignancies. In this study, we investigated the expression profiles of 797 UPS-related genes using HiSeq data from The Cancer Genome Atlas and identified that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. Gene set enrichment analysis revealed that transcriptome signatures involving proliferation, cell cycle, and apoptosis were critically enriched in specimens with elevated PSMD2...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777720/regulation-of-shigella-effector-kinase-ospg-through-modulation-of-its-dynamic-properties
#11
Andrey M Grishin, Kathryn R Barber, Ruo-Xu Gu, D Peter Tieleman, Gary S Shaw, Miroslaw Cygler
Gram-negative pathogens secrete effector proteins into human cells to modulate normal cellular processes and establish a bacterial replication niche. Shigella and pathogenic E. coli possess homologous effector kinases, OspG and NleH1/2, respectively. Upon translocation, OspG but not NleH binds to ubiquitin and a subset of E2~Ub conjugates, which was shown to activate its kinase activity. Here we show that OspG, having a minimal kinase fold, acquired a novel mechanism of regulation of its activity. Binding of the E2~Ub conjugate to OspG not only stimulates its kinase activity but also increases its optimal temperature for activity to match the human body temperature and stabilizes its labile C-terminal domain...
May 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29777712/speckle-type-poz-protein-suppresses-hepatocellular-carcinoma-cell-migration-and-invasion-via-ubiquitin-dependent-proteolysis-of-sumo1-sentrin-specific-peptidase-7
#12
Piyou Ji, Shaohua Liang, Pengtao Li, Chengrong Xie, Jie Li, Kang Zhang, Xuqing Zheng, Min Feng, Qiu Li, Hui Jiao, Xiaoqin Chi, Wenxiu Zhao, Sheng Zhang, Xiaomin Wang
Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777695/proteasome-mediated-protein-degradation-is-enhanced-by-fusion-ubiquitin-with-unstructured-degron
#13
Tomonao Inobe, Masayuki Tsukamoto, Miyuki Nozaki
Methods to induce proteasomal degradation of unwanted proteins are valuable in biomedical studies and thus receive increasing attention. For efficient degradation, the proteasome requires both a ubiquitin tag, which delivers substrates to the proteasome, and an unstructured region, where the proteasome engages the substrate for unfolding and degradation. We fused two degron components into a single molecule to create a fusion protein comprising ubiquitin and Rpn4-derived unstructured region. We demonstrated that the fusion protein retained its function to polyubiquitinate target proteins, thereby inducing more efficient proteasomal target degradation than wild-type ubiquitin in vitro and in cells...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777693/cleavage-of-molybdopterin-synthase-moad-moae-linear-fusion-by-jamm-mpn-domain-containing-metalloprotease-dr0402-from-deinococcus-radiodurans
#14
Yoon-Mo Yang, Young-Bin Won, Chang-Jun Ji, Jung-Hoon Kim, Su-Hyun Ryu, Youn-Ha Ok, Jin-Won Lee
Molybdenum cofactor (Moco), molybdopterin (MPT) complexed with molybdenum, is an essential cofactor required for the catalytic center of diverse enzymes in all domains of life. Since Moco cannot be taken up as a nutrient unlike many other cofactors, Moco requires de novo biosynthesis. During the synthesis of MPT, the sulfur atom on the C-terminus of MoaD is transferred to cyclic pyranopterin monophosphate (cPMP) which is bound in the substrate pocket of MoaE. MoaD is a ubiquitin-like (Ubl) protein and has a C-terminal di-Gly motif which is a common feature of Ubl proteins...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777486/physiological-and-quantitative-proteomic-analyses-unraveling-potassium-deficiency-stress-response-in-alligator-weed-alternanthera-philoxeroides-l-root
#15
Li-Qin Li, Lun Liu, Wei Zhuo, Qian Chen, Sheng Hu, Shuang Peng, Xi-Yao Wang, Yi-Fei Lu, Li-Ming Lu
Physiological and iTRAQ based proteomic analysis provided new insights into potassium deficiency stress response in alligator weed root. Alligator weed (Alternanthera philoxeroides) has a strong ability to adapt to potassium deficiency (LK) stress. Proteomic changes in response to this stress are largely unknown in alligator weed. In this study, we investigated physiological and molecular mechanisms under LK using isobaric tags for relative and absolute quantitation to characterize proteome-level changes in this plant...
May 18, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29777440/mir-27a-b-regulates-liver-regeneration-by-posttranscriptional-modification-of-tmub1
#16
Xiang Lan, Guangyao Li, Hongming Liu, Hangwei Fu, Ping Chen, Menggang Liu
BACKGROUND: Transmembrane and ubiquitin-like domain-containing 1 protein (Tmub1) negatively regulates liver regeneration. However, whether this regulation involves posttranscriptional modification of Tmub1 expression is unknown. AIM: The aim of the study was to investigate whether microRNA (miR)-27a/b regulates posttranscriptional modification of Tmub1 and cell proliferation during liver regeneration. METHODS: Tmub1 mRNA 3'-untranslated region (UTR) sequences were analyzed using online software...
May 17, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29777277/impact-of-muscle-atrophy-on-bone-metabolism-and-bone-strength-implications-for-muscle-bone-crosstalk-with-aging-and-disuse
#17
REVIEW
T Bettis, B-J Kim, M W Hamrick
Bone fractures in older adults are often preceded by a loss of muscle mass and strength. Likewise, bone loss with prolonged bed rest, spinal cord injury, or with exposure to microgravity is also preceded by a rapid loss of muscle mass. Recent studies using animal models in the setting of hindlimb unloading or botulinum toxin (Botox) injection also reveal that muscle loss can induce bone loss. Moreover, muscle-derived factors such as irisin and leptin can inhibit bone loss with unloading, and knockout of catabolic factors in muscle such as the ubiquitin ligase Murf1 or the myokine myostatin can reduce osteoclastogenesis...
May 18, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29777200/a-map-of-the-pgc-1%C3%AE-and-nt-pgc-1%C3%AE-regulated-transcriptional-network-in-brown-adipose-tissue
#18
Ji Suk Chang, Sujoy Ghosh, Susan Newman, J Michael Salbaum
Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α play crucial roles in regulating cold-induced thermogenesis in brown adipose tissue (BAT). PGC-1α and NT-PGC-1α are highly induced by cold in BAT and subsequently bind to and coactivate many transcription factors to regulate expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis. To identify the complete repertoire of PGC-1α and NT-PGC-1α target genes in BAT, we analyzed genome-wide DNA-binding and gene expression profiles...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777060/protease-activated-receptor-1-inhibits-cholesterol-efflux-and-promotes-atherogenesis-via-cullin-3-mediated-degradation-of-the-abca1-transporter
#19
Somasundaram Raghavan, Nikhlesh K Singh, Arul M Mani, Gadiparthi N Rao
Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin-Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3-mediated ubiquitination and degradation of ATP-binding cassette subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29776970/the-e3-ubiquitin-ligase-mib-1-is-necessary-to-form-the-nuclear-halo-in-caenorhabditis-elegans-sperm
#20
Leslie A Herrera, Daniel A Starr
Unlike the classical nuclear envelope with two membranes found in other eukaryotic cells, most nematode sperm nuclei are not encapsulated by membranes. Instead, they are surrounded by a nuclear halo of unknown composition. How the halo is formed and regulated is unknown. We used forward genetics to identify molecular lesions behind three classical fer (fertilization defective) mutations that disrupt the ultrastructure of the Caenorhabditis elegans sperm nuclear halo. We found fer-2 and fer-4 alleles to be nonsense mutations in mib-1...
May 18, 2018: G3: Genes—Genomes—Genetics
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