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https://www.readbyqxmd.com/read/28454355/what-is-known-about-melatonin-chemotherapy-and-altered-gene-expression-in-breast-cancer
#1
Carlos Martínez-Campa, Javier Menéndez-Menéndez, Carolina Alonso-González, Alicia González, Virginia Álvarez-García, Samuel Cos
Melatonin, synthesized in and released from the pineal gland, has been demonstrated by multiple in vivo and in vitro studies to have an oncostatic role in hormone-dependent tumors. Furthermore, several clinical trials point to melatonin as a promising adjuvant molecule to be considered for cancer treatment. In the past few years, evidence of a broader spectrum of action of melatonin as an antitumor agent has arisen; thus, melatonin appears to also have therapeutic effects in several types of hormone-independent cancer, including ovarian, leukemic, pancreatic, gastric and non-small cell lung carcinoma...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453668/a-mass-graph-based-approach-for-the-identification-of-modified-proteoforms-using-top-down-tandem-mass-spectra
#2
Qiang Kou, Si Wu, Nikola Tolic, Ljiljana Paša-Tolic, Yunlong Liu, Xiaowen Liu
Motivation: Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes. Proteoform identification is essential to mapping proteoforms to their biological functions as well as discovering novel proteoforms and new protein functions...
May 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28453390/the-torments-of-the-cohesin-ring
#3
Alap P Chavda, Keven Ang, Dmitri Ivanov
Cohesin is a ring-shaped protein complex which comprises the Smc1, Smc3 and Scc1 subunits. It topologically embraces chromosomal DNA to connect sister chromatids and stabilize chromatin loops. It is required for proper chromosomal segregation, DNA repair and transcriptional regulation. We have recently reported that cohesin rings can adopt a "collapsed" rod-like conformation which is driven by the interaction between the Smc1 and Smc3 coiled coil arms and is regulated by post-translational modifications. The "collapsed" conformation plays a role in cohesin ring assembly and its loading on the DNA...
February 27, 2017: Nucleus
https://www.readbyqxmd.com/read/28453255/characterization-and-identification-of-dityrosine-cross-linked-peptides-using-tandem-mass-spectrometry
#4
Soumya Mukherjee, Eugene A Kapp, Amber Lothian, Anne M Roberts, Yury Vasilev, Berin Boughton, Kevin Jeffrey Barnham, W Mei Kok, Craig A Hutton, Colin L Masters, Ashley Bush, Joseph S Beckman, Somdatta Ghosh Dey, Blaine R Roberts
The use of mass spectrometry coupled with chemical cross-linking of proteins has become a powerful tool for proteins structure and interactions studies. Unlike structural analysis of proteins using chemical reagents specific for lysine or cysteine residues, identification of gas-phase fragmentation patterns of endogenous dityrosine cross-linked peptides have not been investigated. Dityrosine cross-linking in proteins and peptides are clinical markers of oxidative stress, ageing and neurodegenerative diseases including Alzheimer's disease and Parkinson's disease...
April 28, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28447979/reconstitution-of-nucleosomes-with-differentially-isotope-labeled-sister-histones
#5
Stamatios Liokatis
Asymmetrically modified nucleosomes contain the two copies of a histone (sister histones) decorated with distinct sets of Post-translational Modifications (PTMs). They are newly identified species with unknown means of establishment and functional implications. Current analytical methods are inadequate to detect the copy-specific occurrence of PTMs on the nucleosomal sister histones. This protocol presents a biochemical method for the in vitro reconstitution of nucleosomes containing differentially isotope-labeled sister histones...
March 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446731/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#6
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446721/senp3-grants-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#7
Di Wu, Chun-Jie Huang, Faheem Ahmed Khan, Xiao-Fei Jiao, Xiao-Ming Liu, Nuruliarizki Shinta Pandupuspitasari, Rahim Dad Brohi, Li-Jun Huo
Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446710/linear-ubiquitin-chains-enzymes-mechanisms-and-biology
#8
REVIEW
Katrin Rittinger, Fumiyo Ikeda
Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28446635/a-motif-and-amino-acid-bias-bioinformatics-pipeline-to-identify-hydroxyproline-rich-glycoproteins
#9
Kim L Johnson, Andrew M Cassin, Andrew Lonsdale, Antony Bacic, Monika Susanne Doblin, Carolyn J Schultz
Intrinsically disordered proteins (IDPs) are functional proteins that lack a well-defined three dimensional structure. The study of IDPs is a rapidly growing area as the crucial biological functions of more of these proteins are uncovered. In plants, IDPs are implicated in plant stress responses, signalling and regulatory processes. A superfamily of cell wall proteins, the hydroxyproline-rich glycoproteins (HRGPs), have characteristic features of IDPs. Their protein backbones are rich in the disordering amino acid proline, they contain repeated sequence motifs and extensive post-translational modifications (glycosylation) and have been implicated in many biological functions...
April 26, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28446542/a-proteolytic-regulator-controlling-chalcone-synthase-stability-and-flavonoid-biosynthesis-in-arabidopsis
#10
Xuebin Zhang, Carolina Abrahan, Thomas A Colquhoun, Chang-Jun Liu
Flavonoids represent a large family of specialized metabolites involved in plant growth, development and adaptation. Chalcone synthase (CHS) catalyzes the first step of flavonoid biosynthesis by directing carbon flux from general phenylpropanoid metabolism to flavonoid pathway. Despite extensive characterization on its function and transcriptional regulation, the molecular basis governing its post-translational modification is enigmatic. Here, we report the discovery of a proteolytic regulator of CHS, namely KFBCHS, a Kelch domain-containing F-box protein in Arabidopsis...
April 26, 2017: Plant Cell
https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#11
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28445864/tumor-antigen-glycosaminoglycan-modification-regulates-antibody-drug-conjugate-delivery-and-cytotoxicity
#12
Helena C Christianson, Julien A Menard, Vineesh Indira Chandran, Erika Bourseau-Guilmain, Dmitry Shevela, Jon Lidfeldt, Ann-Sofie Månsson, Silvia Pastorekova, Johannes Messinger, Mattias Belting
Aggressive cancers are characterized by hypoxia, which is a key driver of tumor development and treatment resistance. Proteins specifically expressed in the hypoxic tumor microenvironment thus represent interesting candidates for targeted drug delivery strategies. Carbonic anhydrase (CAIX) has been identified as an attractive treatment target as it is highly hypoxia specific and expressed at the cell-surface to promote cancer cell aggressiveness. Here, we find that cancer cell internalization of CAIX is negatively regulated by post-translational modification with chondroitin or heparan sulfate glycosaminoglycan chains...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445788/an-emerging-role-for-the-ribosome-as-a-nexus-for-post-translational-modifications
#13
REVIEW
Deniz Simsek, Maria Barna
The ribosome is one of life's most ancient molecular machines that has historically been viewed as a backstage participant in gene regulation, translating the genetic code across all kingdoms of life in a rote-like fashion. However, recent studies suggest that intrinsic components of the ribosome can be regulated and diversified as a means to intricately control the expression of the cellular proteome. In this review, we discuss advances in the characterization of ribosome post-translational modifications (PTMs) from past to present...
April 22, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28445735/a-design-principle-for-an-autonomous-post-translational-pattern-formation
#14
Shuhei S Sugai, Koji L Ode, Hiroki R Ueda
Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445029/nhs-esters-as-versatile-reactivity-based-probes-for-mapping-proteome-wide-ligandable-hotspots
#15
Carl C Ward, Jordan I Kleinman, Daniel K Nomura
Most of the proteome is considered undruggable oftentimes hindering translational efforts for drug discovery. Identifying previously unknown druggable hotspots in proteins would enable strategies for pharmacologically interrogating these sites with small-molecules. Activity-based protein profiling (ABPP) has arisen as a powerful chemoproteomic strategy that uses reactivity-based chemical probes to map reactive, functional, and ligandable hotspots in complex proteomes, which has enabled inhibitor discovery against various therapeutic protein targets...
April 26, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28442447/detailed-two-dimensional-gel-proteomic-mapping-of-the-feces-of-the-house-dust-mite-dermatophagoides-pteronyssinus-and-comparison-with-d-farinae-reduced-trypsin-protease-content-in-d-pteronyssinus-and-different-isoforms
#16
Tomas Erban, Karel Harant, Jan Hubert
Major domestic mite allergens are present in feces. We present a detailed 2D-E-MS/MS proteomic analysis of the Dermatophagoides pteronyssinus feces. Precise cultivation yielded a pure fecal extract. We detected differences in fecal allergens/digestive enzymes between D. pteronyssinus and D. farinae using 2D-E fingerprinting, including unique information on species-specific protease isoforms. Proteomic analysis was performed by 2D-E coupled with MALDI-TOF/TOF identification. The species-specific differences in the fecal extracts of the mites were attributed to trypsin-like proteases known as group 3 allergens...
April 22, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28441545/targeted-mass-spectrometry-an-emerging-powerful-approach-to-unblock-the-bottleneck-in-phosphoproteomics
#17
REVIEW
Nerea Osinalde, Kerman Aloria, Miren J Omaetxebarria, Irina Kratchmarova
Following the rapid expansion of the proteomics field, the investigation of post translational modifications (PTM) has become extremely popular changing our perspective of how proteins constantly fine tune cellular functions. Reversible protein phosphorylation plays a pivotal role in virtually all biological processes in the cell and it is one the most characterized PTM up to date. During the last decade, the development of phosphoprotein/phosphopeptide enrichment strategies and mass spectrometry (MS) technology has revolutionized the field of phosphoproteomics discovering thousands of new site-specific phosphorylations and unveiling unprecedented evidence about their modulation under distinct cellular conditions...
April 17, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28440894/chromatin-sumoylation-in-heat-stress-to-protect-pause-and-organise-sumo-stress-response-on-chromatin
#18
REVIEW
Einari A Niskanen, Jorma J Palvimo
Post-translational modifications, e.g. SUMO modifications (SUMOylation), provide a mechanism for swiftly changing a protein's activity. Various stress conditions trigger a SUMO stress response (SSR) - a stress-induced rapid change in the conjugation of SUMO to multiple proteins, which predominantly targets nuclear proteins. The SSR has been postulated to protect stressed cells by preserving the functionality of crucial proteins. However, it is unclear how it exerts its protective functions. Interestingly, heat stress (HS) increases SUMOylation of proteins at active promoters and enhancers...
April 25, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28439717/negligible-effect-of-enos-palmitoylation-on-fatty-acid-regulation-of-contraction-in-ventricular-myocytes-from-healthy-and-hypertensive-rats
#19
Chun Li Jin, Yu Na Wu, Ji Hyun Jang, Zai Hao Zhao, Goo Taeg Oh, Sung Joon Kim, Yin Hua Zhang
S-palmitoylation is an important post-translational modification that affects the translocation and the activity of target proteins in a variety of cell types including cardiomyocytes. Since endothelial nitric oxide synthase (eNOS) is known to be palmitoylated and the activity of eNOS is essential in fatty acid-dependent β-oxidation in muscle, we aimed to test whether palmitoylation of eNOS is involved in palmitic acid (PA) regulation of left ventricular (LV) myocyte contraction from healthy (sham) and hypertensive (HTN) rats...
April 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28439035/the-regulation-function-and-detection-of-protein-acetylation-in-bacteria
#20
Valerie J Carabetta, Ileana M Cristea
N(ε)-lysine acetylation is now recognized as an abundant post-translational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of rare acetylation events in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely-tuned via both enzymatic and non-enzymatic mechanisms...
April 24, 2017: Journal of Bacteriology
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