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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/29780465/identification-of-a-selective-dna-ligase-for-accurate-recognition-and-ultrasensitive-quantification-of-n-6-methyladenosine-in-rna-at-one-nucleotide-resolution
#3
Weiliang Liu, Jingli Yan, Zhenhao Zhang, Hongru Pian, Chenghui Liu, Zhengping Li
N 6 -Methyladenosine (m6 A) is the most frequent post-transcriptional modification in RNA, and it plays a critical role in biological processes. The functions of m6 A remain largely unexplored due to a lack of highly sensitive methods to quantitatively determine the m6 A modification fraction at a precise location. Here, we first reveal that T3 DNA ligase has significant selectivity towards the m6 A modification. On the basis of the new finding, we establish an ultrasensitive quantitation assay for accurately determining m6 A at one-nucleotide resolution in RNA...
April 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780463/simultaneous-multiple-single-nucleotide-polymorphism-detection-based-on-click-chemistry-combined-with-dna-encoded-probes
#4
Qian-Yu Zhou, Fang Yuan, Xiao-Hui Zhang, Ying-Lin Zhou, Xin-Xiang Zhang
Single nucleotide polymorphisms (SNPs) are emerging as important biomarkers for disease diagnosis, prognostics and disease pathogenesis. As one type of disease is always connected to several SNP sites, there is great demand for a reliable multiple SNP detection method. Herein, we mimicked a ligation reaction based on DNA ligase and originally utilized an enzyme-free DNA template-directed click reaction for SNP detection. With 5'-alkyne and 3'-azide groups labelled on two oligonucleotide probes, the target DNA-directed Cu(i)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction produced a new DNA strand with a triazole backbone, as a mimic of a DNA phosphodiester linkage...
April 7, 2018: Chemical Science
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/29778533/casein-kinase-ii-phosphorylates-the-c-terminal-region-of-lif1-to-promote-the-lif1-xrs2-interaction-needed-for-non-homologous-end-joining
#7
Kenichiro Matsuzaki, Miki Shinohara
A DNA double strand break (DSB) is one of the most cytotoxic DNA lesions, but it can be repaired by non-homologous end joining (NHEJ) or by homologous recombination. The choice between these two repair pathways depends on the cell cycle stage. Although NHEJ constitutes a simple re-ligation reaction, the regulatory mechanism(s) controlling its activity has not been fully characterized. Lif1 is a regulatory subunit of the NHEJ-specific DNA ligase IV and interacts with Xrs2 of the MRX complex which is a key factor in DSB repair...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777907/novel-snps-of-wnk1-and-akr1c3-are-associated-with-preeclampsia
#8
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/29777277/impact-of-muscle-atrophy-on-bone-metabolism-and-bone-strength-implications-for-muscle-bone-crosstalk-with-aging-and-disuse
#9
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/29777060/protease-activated-receptor-1-inhibits-cholesterol-efflux-and-promotes-atherogenesis-via-cullin-3-mediated-degradation-of-the-abca1-transporter
#10
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
#11
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
https://www.readbyqxmd.com/read/29775763/photoreceptor-mediated-regulation-of-the-cop1-spa-e3-ubiquitin-ligase
#12
REVIEW
Roman Podolec, Roman Ulm
Plants have evolved specific photoreceptors that capture informational cues from sunlight. The phytochrome, cryptochrome, and UVR8 photoreceptors perceive red/far-red, blue/UV-A, and UV-B light, respectively, and control overlapping photomorphogenic responses important for plant growth and development. A major repressor of such photomorphogenic responses is the E3 ubiquitin ligase formed by CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and SUPPRESSOR OF PHYA-105 (SPA) proteins, which acts by regulating the stability of photomorphogenesis-promoting transcription factors...
May 15, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29775751/expression-pattern-and-functional-analysis-of-the-two-ring-box-protein-rbx-in-spermatogenesis-of-chinese-mitten-crab-eriocheir-sinensis
#13
Jia-Shun Zhang, Xue-Jie Li, Lei Yang, Wei-Wei Li, Qun Wang
Studies in E. sinensis have shown that ubiquitination mediated by Cullin-RING E3 ligases (CRLs) plays important roles in spermatogenesis. In other species, CRLs are also essential in cell cycle progression, DNA replication, signal transduction, gene transcription, and development. The catalytic RING component, the RING box protein, is an important part of CRLs. However, there have been few studies on CRLs in crustaceans. In this study, we cloned two RING box protein genes from the Chinese mitten crab, Eriocheir sinensis, termed Es-RBX1 and Es-RBX2 The full length Es-RBX1 cDNA comprises 741 nucleotides, and encodes a protein of 124 amino acid residues, whereas the Es-RBX2 cDNA comprises 1325 nucleotides, and encodes a protein of 110 amino acid residues...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775578/c-terminal-end-directed-protein-elimination-by-crl2-ubiquitin-ligases
#14
Hsiu-Chuan Lin, Chi-Wei Yeh, Yen-Fu Chen, Ting-Ting Lee, Pei-Yun Hsieh, Domnita V Rusnac, Sung-Ya Lin, Stephen J Elledge, Ning Zheng, Hsueh-Chi S Yen
The proteolysis-assisted protein quality control system guards the proteome from potentially detrimental aberrant proteins. How miscellaneous defective proteins are specifically eliminated and which molecular characteristics direct them for removal are fundamental questions. We reveal a mechanism, DesCEND (destruction via C-end degrons), by which CRL2 ubiquitin ligase uses interchangeable substrate receptors to recognize the unusual C termini of abnormal proteins (i.e., C-end degrons). C-end degrons are mostly less than ten residues in length and comprise a few indispensable residues along with some rather degenerate ones...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29773824/rnase-h-assisted-rna-primed-rolling-circle-amplification-for-targeted-rna-sequence-detection
#15
Hirokazu Takahashi, Masahiko Ohkawachi, Kyohei Horio, Toshiro Kobori, Tsunehiro Aki, Yukihiko Matsumura, Yutaka Nakashimada, Yoshiko Okamura
RNA-primed rolling circle amplification (RPRCA) is a useful laboratory method for RNA detection; however, the detection of RNA is limited by the lack of information on 3'-terminal sequences. We uncovered that conventional RPRCA using pre-circularized probes could potentially detect the internal sequence of target RNA molecules in combination with RNase H. However, the specificity for mRNA detection was low, presumably due to non-specific hybridization of non-target RNA with the circular probe. To overcome this technical problem, we developed a method for detecting a sequence of interest in target RNA molecules via RNase H-assisted RPRCA using padlocked probes...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773687/the-role-of-intercalated-cell-nedd4-2-in-bp-regulation-ion-transport-and-transporter-expression
#16
Masayoshi Nanami, Truyen D Pham, Young Hee Kim, Baoli Yang, Roy L Sutliff, Olivier Staub, Janet D Klein, Karen I Lopez-Cayuqueo, Regine Chambrey, Annie Y Park, Xiaonan Wang, Vladimir Pech, Jill W Verlander, Susan M Wall
Background Nedd4-2 is an E3 ubiquitin-protein ligase that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between Nedd4-2 and BP. In this study, we explored the effect of intercalated cell (IC) Nedd4-2 gene ablation on IC transporter abundance and function and on BP. Methods We generated IC Nedd4-2 knockout mice using Cre-lox technology and produced global pendrin/ Nedd4-2 null mice by breeding global Nedd4-2 null ( Nedd4-2-/- ) mice with global pendrin null ( Slc26a4-/- ) mice...
May 17, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29771335/loss-of-fragile-x-protein-fmrp-impairs-homeostatic-synaptic-downscaling-through-tumor-suppressor-p53-and-ubiquitin-e3-ligase-nedd4-2
#17
Kwan Young Lee, Kathryn A Jewett, Hee Jung Chung, Nien-Pei Tsai
Synaptic scaling allows neurons to homeostatically readjust synaptic strength upon chronic neural activity perturbations. Although altered synaptic scaling has been implicated to underlie imbalanced brain excitability in neurological disorders such as autism spectrum disorders and epilepsy, the molecular dysregulation and restoration of synaptic scaling in those diseases have not been demonstrated. Here, we showed that the homeostatic synaptic downscaling is absent in the hippocampal neurons of Fmr1 KO mice, the mouse model of the most common inherited autism, Fragile X Syndrome (FXS)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29770510/scf-sniper-4-controls-the-turnover-of-two-redundant-traf-proteins-in-plant-immunity
#18
Jianhua Huang, Chipan Zhu, Xin Li
In mammals, tumor necrosis factor receptor associated factors (TRAFs) are signaling adaptors that regulate diverse physiological processes, including immunity and stress responses. In Arabidopsis, MUSE13 and MUSE14 are redundant TRAF proteins serving as adaptors in the SCFCRP 1 complex to facilitate the turnover of nucleotide-binding domain and leucine-rich repeats (NLR) immune receptors. Degradation of MUSE13 is inhibited by proteasome inhibitor, suggesting that the MUSE13 stability is controlled by the 26S proteasome...
May 16, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29769720/rspo2-inhibition-of-rnf43-and-znrf3-governs-limb-development-independently-of-lgr4-5-6
#19
Emmanuelle Szenker-Ravi, Umut Altunoglu, Marc Leushacke, Célia Bosso-Lefèvre, Muznah Khatoo, Hong Thi Tran, Thomas Naert, Rivka Noelanders, Amin Hajamohideen, Claire Beneteau, Sergio B de Sousa, Birsen Karaman, Xenia Latypova, Seher Başaran, Esra Börklü Yücel, Thong Teck Tan, Lena Vlaeminck, Shalini S Nayak, Anju Shukla, Katta Mohan Girisha, Cédric Le Caignec, Natalia Soshnikova, Zehra Oya Uyguner, Kris Vleminckx, Nick Barker, Hülya Kayserili, Bruno Reversade
The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling1-3 . Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Functional studies revealed impaired binding to the LGR4/5/6 receptors and the RNF43 and ZNRF3 transmembrane ligases, and reduced WNT potentiation, which correlated with allele severity. Unexpectedly, however, the triple and ubiquitous knockout of Lgr4, Lgr5 and Lgr6 in mice did not recapitulate the known Rspo2 or Rspo3 loss-of-function phenotypes...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769719/klhl22-activates-amino-acid-dependent-mtorc1-signalling-to-promote-tumorigenesis-and-ageing
#20
Jie Chen, Yuhui Ou, Yanyan Yang, Wen Li, Ye Xu, Yuntao Xie, Ying Liu
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids1,2 . Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing2-4 . In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation5,6 . The GATOR1 complex, consisting of DEPDC5, NPRL3 and NPRL2, displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions 7 ...
May 16, 2018: Nature
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