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https://www.readbyqxmd.com/read/28110180/combinatorial-function-of-transcription-factors-and-cofactors
#1
REVIEW
Franziska Reiter, Sebastian Wienerroither, Alexander Stark
Differential gene expression gives rise to the many cell types of complex organisms. Enhancers regulate transcription by binding transcription factors (TFs), which in turn recruit cofactors to activate RNA Polymerase II at core promoters. Transcriptional regulation is typically mediated by distinct combinations of TFs, enabling a relatively small number of TFs to generate a large diversity of cell types. However, how TFs achieve combinatorial enhancer control and how enhancers, enhancer-bound TFs, and the cofactors they recruit regulate RNA Polymerase II activity is not entirely clear...
January 19, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28109749/glycosylation-of-voltage-gated-calcium-channels-in-health-and-disease
#2
REVIEW
Joanna Lazniewska, Norbert Weiss
Voltage-gated calcium channels (VGCCs) are transmembrane proteins that translate electrical activities into intracellular calcium elevations and downstream signaling pathways. They serve essential physiological functions including communication between nerve cells, muscle contraction, cardiac activity, and release of hormones and neurotransmitters. Asparagine-linked glycosylation has emerged as an essential post-translational modification to control the number of channels embedded in the plasma membrane but also their functional gating properties...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28109721/inflammasome-priming-in-sterile-inflammatory-disease
#3
REVIEW
Meghana N Patel, Richard G Carroll, Silvia Galván-Peña, Evanna L Mills, Robin Olden, Martha Triantafilou, Amaya I Wolf, Clare E Bryant, Kathy Triantafilou, Seth L Masters
The inflammasome is a cytoplasmic protein complex that processes interleukins (IL)-1β and IL-18, and drives a form of cell death known as pyroptosis. Oligomerization of this complex is actually the second step of activation, and a priming step must occur first. This involves transcriptional upregulation of pro-IL-1β, inflammasome sensor NLRP3, or the non-canonical inflammasome sensor caspase-11. An additional aspect of priming is the post-translational modification of particular inflammasome constituents...
January 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28109528/specific-enrichment-of-a-targeted-nitrotyrosine-containing-peptide-from-complex-matrices-and-relative-quantification-for-liquid-chromatography-mass-spectrometry-analysis
#4
Yun Yang
Protein tyrosine nitration is considered an important non-enzymatic post-translational modification. In the tyrosine nitration process, 3-nitrotyrosine is formed and recognized as a biomarker of nitrosative/nitrative stress implicated in inflammatory responses and age-related disorders. In view of the complexity of biological samples and the ultra-low abundance of protein-incorporated nitrotyrosine, selective enrichment of nitrotyrosine-containing peptides prior to chromatographic separation is crucial. Herein, I report a simple yet highly specific and efficient enrichment method for nitrotyrosine-containing peptides...
January 15, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28108801/phosphorylation-implications-in-cancer
#5
REVIEW
Vishakha Singh, Mahendra Ram, Rajesh Kumar, Raju Prasad, Birendra Kumar Roy, Kaushal Kumar Singh
Post translational modifications (PTMs) are involved in variety of cellular activities and phosphorylation is one of the most extensively studied PTM, which regulates a number of cellular functions like cell growth, differentiation, apoptosis and cell signaling in healthy condition. However, alterations in phosphorylation pathways result in serious outcomes in the form of diseases, especially cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc...
January 20, 2017: Protein Journal
https://www.readbyqxmd.com/read/28108585/histone-h3k4-and-h3k36-methylation-independently-recruit-the-nua3-histone-acetyltransferase-in-saccharomyces-cerevisiae
#6
Benjamin J E Martin, Kristina L McBurney, Vicki E Maltby, Kristoffer N Jensen, Julie Brind'Amour, LeAnn Howe
Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatin-modifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. In S. cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14, which in vitro bind to H3K4 methylation, H3K36 methylation, and acetylated and crotonylated H3K9 respectively...
January 20, 2017: Genetics
https://www.readbyqxmd.com/read/28107648/parp-1-controls-the-adipogenic-transcriptional-program-by-parylating-c-ebp%C3%AE-and-modulating-its-transcriptional-activity
#7
Xin Luo, Keun Woo Ryu, Dae-Seok Kim, Tulip Nandu, Carlos J Medina, Rebecca Gupte, Bryan A Gibson, Raymond E Soccio, Yonghao Yu, Rana K Gupta, W Lee Kraus
Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPβ, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPβ's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28106845/post-translational-modifications-of-the-tak1-tab-complex
#8
REVIEW
Yusuke Hirata, Miki Takahashi, Tohru Morishita, Takuya Noguchi, Atsushi Matsuzawa
Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family that is activated by growth factors and cytokines such as TGF-β, IL-1β, and TNF-α, and mediates a wide range of biological processes through activation of the nuclear factor-κB (NF-κB) and the mitogen-activated protein (MAP) kinase signaling pathways. It is well established that activation status of TAK1 is tightly regulated by forming a complex with its binding partners, TAK1-binding proteins (TAB1, TAB2, and TAB3)...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#9
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106377/chemical-proteomics-maps-brain-region-specific-activity-of-endocannabinoid-hydrolases
#10
Marc P Baggelaar, Annelot van Esbroeck, Eva van Rooden, Bogdan I Florea, Herman S Overkleeft, Giovanni Marsicano, Francis Chaouloff, Mario van der Stelt
The biosynthetic and catabolic enzymes of the endocannabinoids tightly regulate endocannabinoid-mediated activation of the cannabinoid CB1 receptor. Monitoring the activities of these endocannabinoid hydrolases in different brain regions is, therefore, key to gain insight in spatiotemporal control of CB1 receptor-mediated physiology. We have employed a comparative chemical proteomics approach to quantitatively map the activity profile of endocannabinoid hydrolases in various mouse brain regions at the same time...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28106097/lancl-proteins-are-not-involved-in-lanthionine-synthesis-in-mammals
#11
Chang He, Min Zeng, Debapriya Dutta, Tong Hee Koh, Jie Chen, Wilfred A van der Donk
LanC-like (LanCL) proteins are mammalian homologs of bacterial LanC enzymes, which catalyze the addition of the thiol of Cys to dehydrated Ser residues during the biosynthesis of lanthipeptides, a class of natural products formed by post-translational modification of precursor peptides. The functions of LanCL proteins are currently unclear. A recent proposal suggested that LanCL1 catalyzes the addition of the Cys of glutathione to protein- or peptide-bound dehydroalanine (Dha) to form lanthionine, analogous to the reaction catalyzed by LanC in bacteria...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104714/long-term-biased-%C3%AE-arrestin-signaling-improves-cardiac-structure-and-function-in-dilated-cardiomyopathy
#12
David M Ryba, Jieli Li, Conrad L Cowan, Brenda Russell, Beata M Wolska, R John Solaro
BACKGROUND: -Biased agonism of the angiotensin receptor (AT1R) is known to promote cardiac contractility. Our laboratory indicated that these effects may be due to changes at the level of the myofilaments. However, these signaling mechanisms remain unknown. As a common finding in dilated cardiomyopathy (DCM) is a reduction in the myofilament-Ca(2+)-response, we hypothesized that β-arrestin signaling would increase myofilament-Ca(2+)-responsiveness in a model of familial DCM and improve cardiac function and morphology...
January 19, 2017: Circulation
https://www.readbyqxmd.com/read/28103682/mapping-the-phosphorylation-pattern-of-drosophila-melanogaster-rna-polymerase-ii-carboxyl-terminal-domain-using-ultraviolet-photodissociation-mass-spectrometry
#13
Joshua E Mayfield, Michelle R Robinson, Victoria C Cotham, Seema Irani, Wendy L Matthews, Anjana Ram, David S Gilmour, Joe R Cannon, Yan Jessie Zhang, Jennifer S Brodbelt
Phosphorylation of the C-terminal domain of RNA polymerase II (CTD) plays an essential role in eukaryotic transcription by recruiting transcriptional regulatory factors to the active polymerase. However, the scarcity of basic residues and repetitive nature of the CTD sequence impose a huge challenge for site-specific characterization of phosphorylation, hindering our understanding of this crucial biological process. Herein, we apply LC-UVPD-MS methods to analyze post-translational modification along native sequence CTDs...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103160/yersinia-pestis-acetyltransferase-mediated-dual-acetylation-at-the-serine-and-lysine-residues-enhances-the-auto-ubiquitination-of-ubiquitin-ligase-march8-in-human-cells
#14
Cuiling Li, Daoguang Wang, Xin Lv, Ruirui Jing, Baibin Bi, Xinjun Chen, Jisheng Guo, Fengqin Wang, Shengnan Sun, Kazem M Azadzoi, Jing-Hua Yang
Lysine acetylation is known as a post translational modification (PTM) by histone acetyltransferases (HAT) that modifies histones and non-histone proteins to regulate gene expression. Serine acetylation, however, is reported in mammalian hosts by serine acetyltransferase of Yersinia pestis (YopJ) during infection. The protein target and cellular function of bacterial YopJ in mammalian systems are not fully addressed. Here we report dual acetylation at the serine and lysine residues by transiently expressed serine acetyltransferase YopJ mimicking Y...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28102754/enhancement-of-antibody-functions-through-fc-multiplications
#15
Qun Wang, Yan Chen, Mark Pelletier, Romana Cvitkovic, Jessica Bonnell, Chien-Ying Chang, Adem C Koksal, Ellen O'Connor, Xizhe Gao, Xiang-Qing Yu, Herren Wu, C Kendall Stover, William F Dall'Acqua, Xiaodong Xiao
Antibodies carry out a plethora of functions through their crystallizable fragment (Fc) regions, which can be naturally tuned by the adoption of several isotypes and post-translational modifications. Protein engineering enables further Fc function modulations through modifications of the interactions between the Fc and its functional partners, including FcγR, FcRn, complement complex, and additions of auxiliary functional units. Due to the many functions embedded within the confinement of an Fc, a suitable balance must be maintained for a therapeutic antibody to be effective and safe...
January 19, 2017: MAbs
https://www.readbyqxmd.com/read/28102297/whsc1l1-mediated-egfr-mono-methylation-enhances-the-cytoplasmic-and-nuclear-oncogenic-activity-of-egfr-in-head-and-neck-cancer
#16
Vassiliki Saloura, Theodore Vougiouklakis, Makda Zewde, Xiaolan Deng, Kazuma Kiyotani, Jae-Hyun Park, Yo Matsuo, Mark Lingen, Takehiro Suzuki, Naoshi Dohmae, Ryuji Hamamoto, Yusuke Nakamura
While multiple post-translational modifications have been reported to regulate the function of epidermal growth factor receptor (EGFR), the effect of protein methylation on its function has not been well characterized. In this study, we show that WHSC1L1 mono-methylates lysine 721 in the tyrosine kinase domain of EGFR, and that this methylation leads to enhanced activation of its downstream ERK cascade without EGF stimulation. We also show that EGFR K721 mono-methylation not only affects the function of cytoplasmic EGFR, but also that of nuclear EGFR...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101870/fibrillar-collagens
#17
Jordi Bella, David J S Hulmes
Fibrillar collagens (types I, II, III, V, XI, XXIV and XXVII) constitute a sub-group within the collagen family (of which there are 28 types in humans) whose functions are to provide three-dimensional frameworks for tissues and organs. These networks confer mechanical strength as well as signalling and organizing functions through binding to cellular receptors and other components of the extracellular matrix (ECM). Here we describe the structure and assembly of fibrillar collagens, and their procollagen precursors, from the molecular to the tissue level...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101869/fibrin-formation-structure-and-properties
#18
John W Weisel, Rustem I Litvinov
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101851/importance-of-radioactive-labelling-to-elucidate-inositol-polyphosphate-signalling
#19
REVIEW
Miranda S C Wilson, Adolfo Saiardi
Inositol polyphosphates, in their water-soluble or lipid-bound forms, represent a large and multifaceted family of signalling molecules. Some inositol polyphosphates are well recognised as defining important signal transduction pathways, as in the case of the calcium release factor Ins(1,4,5)P3, generated by receptor activation-induced hydrolysis of the lipid PtdIns(4,5)P2 by phospholipase C. The birth of inositol polyphosphate research would not have occurred without the use of radioactive phosphate tracers that enabled the discovery of the "PI response"...
February 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28100301/high-throughput-screening-of-a-glaxosmithkline-protein-kinase-inhibitor-set-identifies-an-inhibitor-of-human-cytomegalovirus-replication-that-prevents-creb-and-histone-h3-post-translational-modification
#20
Amina S Khan, Matthew J Murray, Catherine M K Ho, William J Zuercher, Matthew B Reeves, Blair L Strang
To identify new compounds with anti-human cytomegalovirus (HCMV) activity and new anti-HCMV targets, we developed a high throughput strategy to screen a GlaxoSmithKline (GSK) Published Kinase Inhibitor Set (PKIS). This collection contains a range of extensively characterized compounds grouped into chemical families (chemotypes). From our screen we identified compounds within chemotypes that impede HCMV replication and identified kinase proteins associated with inhibition of HCMV replication that are potential novel anti-HCMV targets...
January 18, 2017: Journal of General Virology
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