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https://www.readbyqxmd.com/read/28820583/processing-2-methyl-l-tryptophan-through-tandem-transamination-and-selective-oxygenation-initiates-indole-ring-expansion-in-the-biosynthesis-of-thiostrepton
#1
Zhi Lin, Jia Ji, Shuaixiang Zhou, Fang Zhang, Jiequn Wu, Yinlong Guo, Wen Liu
Thiostrepton (TSR), an archetypal member of the family of ribosomally synthesized and post-translationally modified thiopeptide antibiotics, possesses a biologically important quinaldic acid (QA) moiety within the side-ring system of its characteristic thiopeptide framework. QA is derived from an independent L-Trp residue; however, its associated transformation process remains poorly understood. We here report that during the formation of QA, the key expansion of an indole to a quinoline relies on the activities of the pyridoxal-5'-phosphate-dependent protein TsrA and the flavoprotein TsrE...
August 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28820485/disentangling-the-frames-the-state-of-research-on-the-alphavirus-6k-and-tf-proteins
#2
REVIEW
Jolene Ramsey, Suchetana Mukhopadhyay
For 30 years it was thought the alphavirus 6K gene encoded a single 6 kDa protein. However, through a bioinformatics search 10 years ago, it was discovered that there is a frameshifting event and two proteins, 6K and transframe (TF), are translated from the 6K gene. Thus, many functions attributed to the 6K protein needed reevaluation to determine if they properly belong to 6K, TF, or both proteins. In this mini-review, we reevaluate the past research on 6K and put those results in context where there are two proteins, 6K and TF, instead of one...
August 18, 2017: Viruses
https://www.readbyqxmd.com/read/28820317/ulk1-ubiquitylation-is-regulated-by-phosphorylation-on-its-carboxy-terminus
#3
Francesca Nazio, Marianna Carinci, Francesco Cecconi
Autophagy is a highly conserved process that acts sequestering cytoplasmic components for their degradation by the lysosomes. It consists of several sequential steps that have to be finely regulated to ensure both its progression and termination. Post-translational modifications (PTMs) play an important role in regulating ATG proteins function in different stages of autophagy. Recently, we demonstrated that, during prolonged starvation, ULK1 protein is specifically ubiquitylated by NEDD4L, and that this regulation is important to protect cells against excessive autophagy...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820289/recent-advances-in-quantitative-and-chemical-proteomics-for-autophagy-studies
#4
Yin-Kwan Wong, Jianbin Zhang, Zi-Chun Hua, Qingsong Lin, Han-Ming Shen, Jigang Wang
Macroautophagy/autophagy is an evolutionarily well-conserved cellular degradative process with important biological functions that is closely implicated in health and disease. In recent years, quantitative mass spectrometry-based proteomics and chemical proteomics have emerged as important tools for the study of autophagy, through large-scale unbiased analysis of the proteome or through highly specific and accurate analysis of individual proteins of interest. At present, a variety of approaches have been successfully applied, including (i) expression and interaction proteomics for the study of protein post-translational modifications, (ii) investigating spatio-temporal dynamics of protein synthesis and degradation, and (iii) direct determination of protein activity and profiling molecular targets in the autophagic process...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820267/causes-and-significance-of-increased-compound-potency-in-cellular-or-physiological-contexts
#5
Adam G Schwaid, Ivan Cornella-Taracido
Compound potency is a key metric that is often used to drive medicinal chemistry programs. Compound potency is also taken into account when identifying the mechanism of action of compounds whose pharmacological target is unknown, particularly when these compounds are identified in phenotypic screens. Often compound potency is determined from assays using recombinantly generated, purified protein. It is well understood in the medicinal chemistry community that potency measured with recombinant enzyme and potency measured in cell may not entirely coincide...
August 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28820257/residues-comprising-the-enhanced-aromatic-sequon-influence-protein-n-glycosylation-efficiency
#6
Yen-Wen Huang, Hwai-I Yang, Ying-Ta Wu, Tsui-Ling Hsu, Tzu-Wen Lin, Jeffery W Kelly, Chi-Huey Wong
N-glycosylation is an important co- and/or post-translational modification that occurs on the vast majority of the 1/3 of the mammalian proteome that traverses the cellular secretory pathway, regulating glycoprotein folding and functions. Previous studies on the sequence requirements for N-glycosylation have yielded the Asn-X-Ser/Thr (NXS/T) sequon and the enhanced aromatic sequons (Phe-X-Asn-X-Thr and Phe-X-X-Asn-X-Thr) which can be efficiently N-glycosylated. To further investigate the influence of sequence variation on N-glycosylation efficiency in the context of a 5-residue enhanced aromatic sequon, we used the human CD2 adhesion domain (hCD2ad) to screen the i-2, i-1, i+1 and i+2 residues flanking Asn at the i position...
August 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28820180/osteogenesis-imperfecta
#7
REVIEW
Joan C Marini, Antonella Forlino, Hans Peter Bächinger, Nick J Bishop, Peter H Byers, Anne De Paepe, Francois Fassier, Nadja Fratzl-Zelman, Kenneth M Kozloff, Deborah Krakow, Kathleen Montpetit, Oliver Semler
Skeletal deformity and bone fragility are the hallmarks of the brittle bone dysplasia osteogenesis imperfecta. The diagnosis of osteogenesis imperfecta usually depends on family history and clinical presentation characterized by a fracture (or fractures) during the prenatal period, at birth or in early childhood; genetic tests can confirm diagnosis. Osteogenesis imperfecta is caused by dominant autosomal mutations in the type I collagen coding genes (COL1A1 and COL1A2) in about 85% of individuals, affecting collagen quantity or structure...
August 18, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28819722/carbon-and-amide-detect-backbone-assignment-methods-of-a-novel-repeat-protein-from-the-staphylocoagulase-in-s-aureus
#8
Markus Voehler, Maddur Appajaiah Ashoka, Jens Meiler, Paul E Bock
The C-terminal repeat domain of staphylocoagulase that is secreted by the S. aureus is believed to play an important role interacting with fibrinogen and promotes blood clotting. To study this interaction by NMR, full assignment of each amide residue in the HSQC spectrum was required. Despite of the short sequence of the repeat construct, the HSQC spectrum contained a substantial amount of overlapped and exchange broadened resonances, indicating little secondary or tertiary structure. This caused severe problems while using the conventional, amide based NMR method for the backbone assignment...
August 17, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28819388/role-of-y-box-protein-1-in-cancer-as-potential-biomarker-and-novel-therapeutic-target
#9
REVIEW
Pramod Kumar Maurya, Alok Mishra, Birendra Singh Yadav, Swati Singh, Prashant Kumar, Amit Chaudhary, Shweta Srivastava, Suriya Narayan Murugesan, Ashutosh Mani
The Y-box binding protein (YB-1) is known to be a multifunctional transcription and translation factor during expression of several proteins. It is a vital oncoprotein that regulates cancer cell progression and proliferation. YB-1 is over-expressed in various human cancers such as breast cancer, colon cancer, lung cancer, gastric cancer, oesophageal cancer and glioblastoma. Nuclear expression of YB-1 is found to be associated with multidrug resistance and cancer cell progression. YB-1 is reported to regulate many cellular signalling pathways in different types of cancer proliferation...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819289/escrt-iii-membrane-trafficking-misregulation-contributes-to-fragile-x-syndrome-synaptic-defects
#10
Dominic J Vita, Kendal Broadie
The leading cause of heritable intellectual disability (ID) and autism spectrum disorders (ASD), Fragile X syndrome (FXS), is caused by loss of the mRNA-binding translational suppressor Fragile X Mental Retardation Protein (FMRP). In the Drosophila FXS disease model, we found FMRP binds shrub mRNA (human Chmp4) to repress Shrub expression, causing overexpression during the disease state early-use critical period. The FXS hallmark is synaptic overelaboration causing circuit hyperconnectivity. Testing innervation of a central brain learning/memory center, we found FMRP loss and Shrub overexpression similarly increase connectivity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819257/cytolytic-dna-vaccine-encoding-lytic-perforin-augments-the-maturation-of-and-antigen-presentation-by-dendritic-cells-in-a-time-dependent-manner
#11
Danushka K Wijesundara, Wenbo Yu, Ben J C Quah, Preethi Eldi, John D Hayball, Kerrilyn R Diener, Ilia Voskoboinik, Eric J Gowans, Branka Grubor-Bauk
The use of cost-effective vaccines capable of inducing robust CD8(+) T cell immunity will contribute significantly towards the elimination of persistent viral infections and cancers worldwide. We have previously reported that a cytolytic DNA vaccine encoding an immunogen and a truncated mouse perforin (PRF) protein significantly augments anti-viral T cell (including CD8(+) T cell) immunity. Thus, the current study investigated whether this vaccine enhances activation of dendritic cells (DCs) resulting in greater priming of CD8(+) T cell immunity...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819166/histone-protein-deacetylase-11-targeting-promotes-foxp3-treg-function
#12
Jianbing Huang, Liqing Wang, Satinder Dahiya, Ulf H Beier, Rongxiang Han, Arabinda Samanta, Joel Bergman, Eduardo M Sotomayor, Edward Seto, Alan P Kozikowski, Wayne W Hancock
Current interest in Foxp3+ T-regulatory (Treg) cells as therapeutic targets in transplantation is largely focused on their harvesting pre-transplant, expansion and infusion post-transplantation. An alternate strategy of pharmacologic modulation of Treg function using histone/protein deacetylase inhibitors (HDACi) may allow more titratable and longer-term dosing. However, the effects of broadly acting HDACi vary, such that HDAC isoform-selective targeting is likely required. We report data from mice with constitutive or conditional deletion of HDAC11 within Foxp3+ Treg cells, and their use, along with small molecule HDAC11 inhibitors, in allograft models...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819135/ribosomal-transcription-is-regulated-by-pgc-1alpha-and-disturbed-in-huntington-s-disease
#13
Sarah Jesse, Hanna Bayer, Marius C Alupei, Martina Zügel, Medhanie Mulaw, Francesca Tuorto, Silke Malmsheimer, Karmveer Singh, Jürgen Steinacker, Uwe Schumann, Albert C Ludolph, Karin Scharffetter-Kochanek, Anke Witting, Patrick Weydt, Sebastian Iben
PGC-1α is a versatile inducer of mitochondrial biogenesis and responsive to the changing energy demands of the cell. As mitochondrial ATP production requires proteins that derive from translation products of cytosolic ribosomes, we asked whether PGC-1α directly takes part in ribosomal biogenesis. Here, we show that a fraction of cellular PGC-1α localizes to the nucleolus, the site of ribosomal transcription by RNA polymerase I. Upon activation PGC-1α associates with the ribosomal DNA and boosts recruitment of RNA polymerase I and UBF to the rDNA promoter...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819043/increased-acetylation-of-microtubules-rescues-human-tau-induced-microtubule-defects-and-neuromuscular-junction-abnormalities-in-drosophila
#14
Chuan-Xi Mao, Xue Wen, Shan Jin, Yong Q Zhang
Tau normally associates with and stabilizes microtubules (MTs), but is hyperphosphorylated and aggregated into neurofibrillary tangles in Alzheimer's disease and related neurodegenerative diseases, which are collectively known as tauopathies. MTs are regulated by different forms of post-translational modification including acetylation; acetylated MTs represent a more stable microtubule population. In our previous study, we show that inhibition of histone deacetylase 6 (HDAC6), which deacetylates tubulin at lysine 40, rescues defects in MTs and in neuromuscular junction growth caused by tau overexpression...
August 17, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28818370/overexpression-of-vpeifp1-a-novel-f-box-kelch-repeat-protein-from-wild-chinese-vitis-pseudoreticulata-confers-higher-tolerance-to-powdery-mildew-by-inducing-thioredoxin-z-proteolysis
#15
Jie Wang, Wenkong Yao, Lei Wang, Fuli Ma, Weihuo Tong, Chen Wang, Rui Bao, Changyue Jiang, Yazhou Yang, Jianxia Zhang, Yan Xu, Xiping Wang, Chaohong Zhang, Yuejin Wang
An F-box protein (VpEIFP1) induced by Erysiphe necator was isolated from Vitis pseudoreticulata, a wild Chinese grapevine species naturally resistant to powdery mildew (PM). It contains an F-box domain and two Kelch-repeat motifs. Expression profiles indicate the VpEIFP1 is strongly induced at both transcriptional and translational levels by PM infection. A subcellular localisation assay showed that VpEIFP1 is predominantly located in the nucleus and cytoplasm. Overexpression of VpEIFP1 accelerated the accumulation of hydrogen peroxide (H2O2) and up-regulated the expressions of ICS2, NPR1 and PR1 involved in defence responses, resulting in suppression of PM germination and growth...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28817801/a-sensitized-igf1-treatment-restores-corticospinal-axon-dependent-functions
#16
Yuanyuan Liu, Xuhua Wang, Wenlei Li, Qian Zhang, Yi Li, Zicong Zhang, Junjie Zhu, Bo Chen, Philip R Williams, Yiming Zhang, Bin Yu, Xiaosong Gu, Zhigang He
A major hurdle for functional recovery after both spinal cord injury and cortical stroke is the limited regrowth of the axons in the corticospinal tract (CST) that originate in the motor cortex and innervate the spinal cord. Despite recent advances in engaging the intrinsic mechanisms that control CST regrowth, it remains to be tested whether such methods can promote functional recovery in translatable settings. Here we show that post-lesional AAV-assisted co-expression of two soluble proteins, namely insulin-like growth factor 1 (IGF1) and osteopontin (OPN), in cortical neurons leads to robust CST regrowth and the recovery of CST-dependent behavioral performance after both T10 lateral spinal hemisection and a unilateral cortical stroke...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817688/the-extremely-divergent-maternally-and-paternally-transmitted-mitochondrial-genomes-are-co-expressed-in-somatic-tissues-of-two-freshwater-mussel-species-with-doubly-uniparental-inheritance-of-mtdna
#17
Sophie Breton, Karim Bouvet, Gabrielle Auclair, Stéphanie Ghazal, Bernard E Sietman, Nathan Johnson, Stefano Bettinazzi, Donald T Stewart, Davide Guerra
Freshwater mussel species with doubly uniparental inheritance (DUI) of mtDNA are unique because they are naturally heteroplasmic for two extremely divergent mtDNAs with ~50% amino acid differences for protein-coding genes. The paternally-transmitted mtDNA (or M mtDNA) clearly functions in sperm in these species, but it is still unknown whether it is transcribed when present in male or female soma. In the present study, we used PCR and RT-PCR to detect the presence and expression of the M mtDNA in male and female somatic and gonadal tissues of the freshwater mussel species Venustaconcha ellipsiformis and Utterbackia peninsularis (Unionidae)...
2017: PloS One
https://www.readbyqxmd.com/read/28817687/morphologic-phenotypic-and-transcriptomic-characterization-of-classically-and-alternatively-activated-canine-blood-derived-macrophages-in-vitro
#18
Franziska Heinrich, Annika Lehmbecker, Barbara B Raddatz, Kristel Kegler, Andrea Tipold, Veronika M Stein, Arno Kalkuhl, Ulrich Deschl, Wolfgang Baumgärtner, Reiner Ulrich, Ingo Spitzbarth
Macrophages are a heterogeneous cell population playing a pivotal role in tissue homeostasis and inflammation, and their phenotype strongly depends on the micromilieu. Despite its increasing importance as a translational animal model for human diseases, there is a considerable gap of knowledge with respect to macrophage polarization in dogs. The present study comprehensively investigated the morphologic, phenotypic, and transcriptomic characteristics of unstimulated (M0), M1- (GM-CSF, LPS, IFNγ-stimulated) and M2- (M-CSF, IL-4-stimulated)-polarized canine blood-derived macrophages in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28817102/anticancer-activity-of-ramalin-a-secondary-metabolite-from-the-antarctic-lichen-ramalina-terebrata-against-colorectal-cancer-cells
#19
Sung-Suk Suh, Tai Kyoung Kim, Jung Eun Kim, Ju-Mi Hong, Trang Thu Thi Nguyen, Se Jong Han, Ui Joung Youn, Joung Han Yim, Il-Chan Kim
Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116...
August 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28816645/a-systems-model-of-parkinson-s-disease-using-biochemical-systems-theory
#20
Hemalatha Sasidharakurup, Nidheesh Melethadathil, Bipin Nair, Shyam Diwakar
Parkinson's disease (PD), a neurodegenerative disorder, affects millions of people and has gained attention because of its clinical roles affecting behaviors related to motor and nonmotor symptoms. Although studies on PD from various aspects are becoming popular, few rely on predictive systems modeling approaches. Using Biochemical Systems Theory (BST), this article attempts to model and characterize dopaminergic cell death and understand pathophysiology of progression of PD. PD pathways were modeled using stochastic differential equations incorporating law of mass action, and initial concentrations for the modeled proteins were obtained from literature...
August 2017: Omics: a Journal of Integrative Biology
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