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https://www.readbyqxmd.com/read/28723107/chemical-approaches-to-investigate-labile-peptide-and-protein-phosphorylation
#1
Anett Hauser, Martin Penkert, Christian P R Hackenberger
Protein phosphorylation is by far the most abundant and most studied post-translational modification (PTM). For a long time, phosphate monoesters of serine (pSer), threonine (pThr), and tyrosine (pTyr) have been considered as the only relevant forms of phosphorylation in organisms. Recently, several research groups have dedicated their efforts to the investigation of other, less characterized phosphoamino acids as naturally occurring PTMs. Such apparent peculiar phosphorylations include the phosphoramidates of histidine (pHis), arginine (pArg), and lysine (pLys), the phosphorothioate of cysteine (pCys), and the anhydrides of pyrophosphorylated serine (ppSer) and threonine (ppThr)...
July 19, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28722276/identification-and-functional-analysis-of-an-adamtsl1-variant-associated-with-a-complex-phenotype-including-congenital-glaucoma-craniofacial-and-other-systemic-features-in-a-three-generation-human-pedigree
#2
Kathryn Hendee, Lauren Weiping Wang, Linda M Reis, Gregory M Rice, Suneel S Apte, Elena V Semina
Developmental glaucoma can occur as an isolated or syndromic condition and is genetically heterogeneous. We describe a three-generation family affected with developmental glaucoma, myopia, and/or retinal defects associated with variable craniofacial/dental, auditory, brain, renal, and limb anomalies. Whole exome sequencing identified a heterozygous c.124T> C, p.(Trp42Arg) allele in ADAMTSL1; co-segregation analysis confirmed the presence of this allele in four affected family members. The mutation affects a highly conserved residue and is strongly predicted to have a deleterious effect on protein function...
July 19, 2017: Human Mutation
https://www.readbyqxmd.com/read/28722191/a-chemoproteomics-approach-to-investigate-phosphopantetheine-transferase-activity-at-the-cellular-level
#3
Sho Konno, Fumihiro Ishikawa, Takehiro Suzuki, Naoshi Dohmae, Hideaki Kakeya, Genzoh Tanabe
Phosphopantetheinylation is an essential post-translational protein modification to primary and secondary metabolic pathways that ensures bacterial cell viability and virulence, and it is used in the production of many pharmaceuticals. Traditional methods have not provided a comprehensive understanding of these modifications. Using chemical proteomic probes for adenylation and thiolation domains in nonribosomal peptide synthetases (NRPSs), we applied chemoproteomics to survey and validate the cellular activity of 4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a potent and selective small molecule 4'-phosphopantetheinyl transferase (PPTase) inhibitor, which attenuates secondary metabolism and viability of bacterial cells...
July 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28721671/front-end-electron-transfer-dissociation-coupled-to-a-21-tesla-ft-icr-mass-spectrometer-for-intact-protein-sequence-analysis
#4
Chad R Weisbrod, Nathan K Kaiser, John E P Syka, Lee Early, Christopher Mullen, Jean-Jacques Dunyach, A Michelle English, Lissa C Anderson, Greg T Blakney, Jeffrey Shabanowitz, Christopher L Hendrickson, Alan G Marshall, Donald F Hunt
High resolution mass spectrometry is a key technology for in-depth protein characterization. High-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) enables high-level interrogation of intact proteins in the most detail to date. However, an appropriate complement of fragmentation technologies must be paired with FTMS to provide comprehensive sequence coverage, as well as characterization of sequence variants, and post-translational modifications. Here we describe the integration of front-end electron transfer dissociation (FETD) with a custom-built 21 tesla FT-ICR mass spectrometer, which yields unprecedented sequence coverage for proteins ranging from 2...
July 18, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28717191/mln4924-pevonedistat-a-protein-neddylation-inhibitor-suppresses-proliferation-and-migration-of-human-clear-cell-renal-cell-carcinoma
#5
Shuai Tong, Yang Si, Hefen Yu, Lingqiang Zhang, Ping Xie, Wenguo Jiang
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717010/phosphorylation-of-the-kainate-receptor-kar-auxiliary-subunit-neto2-at-serine-409-regulates-synaptic-targeting-of-the-kar-subunit-gluk1
#6
Richa Madan Lomash, Nengyin Sheng, Yan Li, Roger A Nicoll, Katherine W Roche
Synaptic strength at excitatory synapses is determined by the presence of glutamate receptors (i.e. AMPA, NMDA and kainate receptors) at the synapse. Synaptic strength is modulated by multiple factors including assembly of different receptor subunits, interaction with auxiliary subunits and post translational modifications of either the receptors or their auxiliary subunits. Using mass spectrometry, we find that the intracellular region of neuropilin and tolloid-like proteins (Neto)1 and Neto2, the auxiliary subunits of KARs are phosphorylated by multiple kinases in vitro...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716105/characterization-of-four-rice-uev1-genes-required-for-lys63-linked-polyubiquitination-and-distinct-functions
#7
Qian Wang, Yuepeng Zang, Xuan Zhou, Wei Xiao
BACKGROUND: The error-free branch of the DNA-damage tolerance (DDT) pathway is orchestrated by Lys63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA), and this polyubiquitination is mediated by a Ubc13-Uev complex in yeast. We have previously cloned OsUBC13 from rice, whose product functions as an E2 to promote Lys63-linked ubiquitin chain assembly in the presence of yeast or human Uev. RESULTS: Here we identify four highly conserved UEV1 genes in rice whose products are able to form stable heterodimers with OsUbc13 and mediate Lys63-linked ubiquitin chain assembly...
July 17, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28714959/o-glcnacylation-modulates-bmi-1-protein-stability-and-potential-oncogenic-function-in-prostate-cancer
#8
Y Li, L Wang, J Liu, P Zhang, M An, C Han, Y Li, X Guan, K Zhang
The Polycomb group transcriptional repressor Bmi-1 often overexpressed and participated in stem cells self-renewal and tumorigenesis initiating of prostate cancer. In this progression, Bmi-1 protein was regulated by transcription and post-translational modifications (PTMs). Nobly, the underlying PTMs regulation of Bmi-1 is poorly known. Here we use co-immunoprecipitation show that in C4-2 cell line, Bmi-1 directly interacted with OGT which is the only known enzyme catalyzed the O-GlcNAcylation in human. Furthermore, we identified that Ser255 is the site for Bmi-1 O-GlcNAcylation, and O-GlcNAcylation promoted Bmi-1 protein stability and its oncogenic activity...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28714192/secreted-tumor-antigens-immune-biomarkers-for-diagnosis-and-therapy
#9
REVIEW
Els N Meeusen, Elgene Lim, Suresh Mathivanan
With the advent of immunotherapies for cancer, there is growing interest in the identification of tumor antigens. Tumor antigens are self-molecules altered through genetic mutations (neoantigens), protein truncation, protein misfolding or abnormal post translational modifications. To induce an immune response, tumor antigens need to be secreted into the tumor environment and presented to the immune system in the draining lymph nodes, resulting in the generation of tumor-specific effector cells and antibodies...
July 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28714086/n-glycan-content-modulates-kainate-receptor-functional-properties
#10
Claire G Vernon, Bryan A Copits, Jacob R Stolz, Yomayra F Guzmán, Geoffrey T Swanson
Ionotropic glutamate receptors (iGluRs) are tetrameric proteins with between 4 and 12 consensus sites for N-glycosylation on each subunit, which potentially allows for a high degree of structural diversity conferred by this post-translational modification. N-glycosylation is required for proper folding of iGluRs in mammalian cells, but the impact of oligosaccharides on the function of successfully folded receptors is less clear. Glycan moieties are large, polar, occasionally charged, and mediate many protein-protein interactions throughout the nervous system...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28713906/chronic-administration-of-sumo%C3%A2-1-has-negative-effects-on-novel-object-recognition-memory-as-well-as-cell-proliferation-and-neuroblast-differentiation-in-the-mouse-dentate-gyrus
#11
Dae Young Yoo, Dae Won Kim, Hyun Jung Kwon, Hyo Young Jung, Sung Min Nam, Jong Whi Kim, Jin Young Chung, Moo-Ho Won, Yeo Sung Yoon, Soo Young Choi, In Koo Hwang
Post‑translational modifications have been associated with developmental and aging processes, as well as in the pathogenesis of certain diseases. The present study aimed to investigate the effects of small ubiquitin‑like modifier 1 (SUMO‑1) on hippocampal dependent memory function, cell proliferation and neuroblast differentiation. To facilitate the delivery of SUMO‑1 into hippocampal neurons, a transactivator of transcription (Tat)‑SUMO‑1 fusion protein was constructed and mice were divided into two groups: A vehicle (Tat peptide)‑treated group and a Tat‑SUMO‑1‑treated group...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713891/hypothermia-exerts-early-neuroprotective-effects-involving-protein-conjugation-of-sumo%C3%A2-2-3-in-a-rat-model-of-middle-cerebral-artery-occlusion
#12
Gang Li, Xiaozhi Liu, Zhiguo Su, Dong Zhang
How hypothermia serves an early protective role against cerebral ischemia remains to be determined. The small ubiquitin‑related modifier protein (SUMO) functions as a post‑translational modification system and SUMO‑2/3 subtypes are often activated in early stress. The present study investigated changes in the protein level of SUMO using western blotting and immunocytochemistry when neurons were exposed to oxygen‑glucose deprivation (OGD) in vitro, as well as in a rat model of middle cerebral artery occlusion (MCAO) in vivo...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712943/sex-and-brain-region-specific-effects-of-prenatal-stress-and-lead-exposure-on-permissive-and-repressive-post-translational-histone-modifications-from-embryonic-development-through-adulthood
#13
G Varma, M Sobolewski, D A Cory-Slechta, J S Schneider
Developmental exposure to prenatal stress (PS) and lead (Pb) can affect brain development and adversely influence behavior and cognition. Epigenetic-based gene regulation is crucial for normal brain development and mis-regulation, in any form, can result in neurodevelopmental disorders. Post-translational histone modifications (PTHMs) are an integral and dynamic component of the epigenetic machinery involved in gene regulation. Exposures to Pb and/or PS may alter PTHM profiles, promoting lifelong alterations in brain function observed following Pb±PS exposure...
July 13, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#14
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28711789/towards-a-better-understanding-of-protein-changes-in-common-bean-under-drought-a-case-study-of-n-glycoproteins
#15
Tanja Zadražnik, Anders Moen, Wolfgang Egge-Jacobsen, Vladimir Meglič, Jelka Šuštar-Vozlič
Drought is one of the major abiotic stress conditions limiting crop growth and productivity. Glycosylation of proteins is very important post-translational modification that is involved in many physiological functions and biological pathways. To understand the involvement of N-glycoproteins in the mechanism of drought response in leaves of common bean, a proteomic approach using lectin affinity chromatography, SDS-PAGE and LC-MS/MS was applied. Quantification of N-glycoproteins was performed using MaxQuant with a label free quantification approach...
July 5, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28710419/generation-of-clade-and-symbiont-specific-antibodies-to-characterize-marker-molecules-during-cnidaria-symbiodinium-endosymbiosis
#16
Kao-Jean Huang, Zi-Yu Huang, Ching-Yen Lin, Li-Hsueh Wang, Pin-Hsiang Chou, Chii-Shiarng Chen, Hsing-Hui Li
The endosymbiosis between cnidarians and dinoflagellates is responsible for the formation of coral reefs. Changes in molecules have been identified during the process of cnidaria-Symbiodinium endosymbiosis. However, the complexity of the molecular interaction has prevented the establishment of a mechanistic explanation of cellular regulation in this mutualistic symbiosis. To date, no marker molecules have been identified to specifically represent the symbiotic status. Because the endosymbiotic association occurs in the symbiotic gastrodermal cells (SGCs), whole cells of isolated SGCs were used as an antigen to generate monoclonal antibodies (mAb) to screen possible molecular candidates of symbiotic markers...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710288/post-transcriptional-control-of-gene-expression-following-stress-the-role-of-rna-binding-proteins
#17
REVIEW
Robert Harvey, Veronica Dezi, Mariavittoria Pizzinga, Anne E Willis
The ability of mammalian cells to modulate global protein synthesis in response to cellular stress is essential for cell survival. While control of protein synthesis is mediated by the regulation of eukaryotic initiation and elongation factors, RNA-binding proteins (RBPs) provide a crucial additional layer to post-transcriptional regulation. RBPs bind specific RNA through conserved RNA-binding domains and ensure that the information contained within the genome and transcribed in the form of RNA is exported to the cytoplasm, chemically modified, and translated prior to folding into a functional protein...
July 14, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28710278/phosphorylation-of-human-aquaporin-2-aqp2-allosterically-controls-its-interaction-with-the-lysosomal-trafficking-protein-lip5
#18
Jennifer Virginia Roche, Sabeen Survery, Stefan Kreida, Veronika Nesverova, Henry Ampah-Korsah, Maria Gourdon, Peter M T Deen, Susanna Toernroth-Horsefield
The interaction between the renal water channel aquaporin-2 (AQP2) and the lysosomal trafficking regulator-interacting protein LIP5 targets AQP2 to multivesicular bodies and facilitates lysosomal degradation. This interaction is part of a process which controls AQP2 apical membrane abundance in a vasopressin-dependent manner, allowing for urine volume adjustment. Vasopressin regulates phosphorylation at four sites within the AQP2 C-terminus (S256, S261, S264, T269), of which S256 is crucial and sufficient for AQP2 translocation from storage vesicles to the apical membrane...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28710277/phosphorylation-of-the-type-ii-transmembrane-serine-protease-tmprss13-in-hepatocyte-growth-factor-activator-inhibitor-1-and-2-mediated-cell-surface-localization
#19
Andrew S Murray, Fausto A Varela, Thomas E Hyland, Andrew J Schoenbeck, Jordan M White, Lauren M Tanabe, Sokol V Todi, Karin List
TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. While various TTSPs have been characterized in detail biochemically and functionally, the basic properties of TMPRSS13 remain unclear. Here, we investigate the activation, inhibition, posttranslational modification, and localization of TMPRSS13. We show that TMPRSS13 is a glycosylated, active protease and that its own proteolytic activity mediates zymogen cleavage. Full-length, active TMPRSS13 exhibits impaired cell-surface expression in the absence of the cognate Kunitz-type serine protease inhibitors, hepatocyte growth factor activator inhibitor (HAI)-1 or HAI-2...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28709899/prediction-of-protein-n-formylation-using-the-composition-of-k-spaced-amino-acid-pairs
#20
Zhe Ju, Jun-Zhe Cao
As one of important protein post-translational modifications, N-formylation has been reported to be involved in various biological processes. The accurate identification of N-formylation sites is crucial for understanding the underlying mechanisms of N-formylation. Since the traditional experimental methods are generally labor-intensive and expensive, it is important to develop computational methods to predict N-formylation sites. In this paper, a predictor named NformPred is proposed to improve the prediction of N-formylation sites by using composition of k-spaced amino acid pairs encoding scheme and support vector machine algorithm...
July 11, 2017: Analytical Biochemistry
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