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https://www.readbyqxmd.com/read/28319808/identifying-regulatory-posttranslational-modifications-of-pd-l1-a-focus-on-monoubiquitinaton
#1
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
A set of high-affinity, high-specificity posttranslational modification (PTM) enrichment tools was developed to generate an unbiased snapshot of four key PTM profiles (tyrosine phosphorylation, acetylation, ubiquitination, and SUMOylation 2/3) for the clinically important protein programmed cell death ligand 1 (PD-L1). The results showed that epidermal growth factor (EGF) treatment induced tyrosine phosphorylation, acetylation, and ubiquitination of PD-L1. Further characterization of EGF-induced PD-L1 ubiquitination revealed a significant increase in mono- and multiubiquitination of PD-L1 that occurred on glycosylated PD-L1...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28300602/yeats-domain-a-histone-acylation-reader-in-health-and-disease
#2
REVIEW
Dan Zhao, Yuanyuan Li, Xiaozhe Xiong, Zhonglei Chen, Haitao Li
Histone post-translational modifications (PTMs) carry an epigenetic layer of message to regulate diverse cellular processes at the chromatin level. Many of these PTMs are selectively recognized by dedicated effector proteins for normal cell growth and development, while dysregulation of these recognition events is often implicated in human diseases, notably cancer. Thus, it is fundamentally important to elucidate the regulatory mechanism(s) underlying readout of PTMs on histones. The YEATS domain is an emerging reader module that selectively recognizes histone lysine acylation with a preference for crotonylation over acetylation...
March 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28299649/covalent-modifications-of-runx-proteins-structure-affects-function
#3
Ezra Blumenthal, Sarah Greenblatt, Guang Huang, Koji Ando, Ye Xu, Stephen D Nimer
The RUNX family of transcription factors plays important roles in tissue-specific gene expression. Many of their functions depend on specific post-translational modifications (PTMs), and in this review, we describe how PTMs govern RUNX DNA binding, transcriptional activity, protein stability, cellular localization, and protein-protein interactions. We also report how these processes can be disrupted in disease settings. Finally, we describe how alterations of RUNX1, or the enzymes that catalyze its post-translational modifications, contribute to hematopoietic malignancies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28298630/proteomic-analysis-of-proteome-and-histone-post-translational-modifications-in-heat-shock-protein-90-inhibition-mediated-bladder-cancer-therapeutics
#4
Qingdi Quentin Li, Jian-Jiang Hao, Zheng Zhang, L Spencer Krane, Kai H Hammerich, Thomas Sanford, Jane B Trepel, Len Neckers, Piyush K Agarwal
Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293301/histone-peptide-microarray-screen-of-chromo-and-tudor-domains-defines-new-histone-lysine-methylation-interactions
#5
Erin K Shanle, Stephen A Shinsky, Joseph B Bridgers, Narkhyun Bae, Cari Sagum, Krzysztof Krajewski, Scott B Rothbart, Mark T Bedford, Brian D Strahl
BACKGROUND: Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized "reader" domains. Despite efforts to elucidate reader domain-PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28289760/pten-proteoforms-in-biology-and-disease
#6
REVIEW
Prerna Malaney, Vladimir N Uversky, Vrushank Davé
Proteoforms are specific molecular forms of protein products arising from a single gene that possess different structures and different functions. Therefore, a single gene can produce a large repertoire of proteoforms by means of allelic variations (mutations, indels, SNPs), alternative splicing and other pre-translational mechanisms, post-translational modifications (PTMs), conformational dynamics, and functioning. Resulting proteoforms that have different sizes, alternative splicing patterns, sets of post-translational modifications, protein-protein interactions, and protein-ligand interactions, might dramatically increase the functionality of the encoded protein...
March 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28286521/pulling-a-ligase-out-of-a-hat-pcaf-mediates-ubiquitination-of-the-class-ii-transactivator
#7
Julie E Morgan, Susanna F Greer
The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the "master regulator" of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region...
2017: International Journal of Cell Biology
https://www.readbyqxmd.com/read/28286085/hspa5-gene-encoding-hsp70-chaperone-bip-in-the-endoplasmic-reticulum
#8
REVIEW
Jie Wang, Jessica Lee, David Liem, Peipei Ping
The HSPA5 gene (Ensembl ID: ENSG00000044574 (WTSI/EMBL-EBI, 2015)) encodes the binding immunoglobulin protein (BiP), an Hsp70 family chaperone localized in the ER lumen. As a highly conserved molecular chaperone, BiP assists in a wide range of folding processes via its two structural domains, a nucleotide-binding domain (NBD) and substrate-binding domain (SBD). BiP is also an essential component of the translocation machinery for protein import into the ER, a regulator for Ca(2+) homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane...
March 7, 2017: Gene
https://www.readbyqxmd.com/read/28281873/resolving-the-micro-heterogeneity-and-structural-integrity-of-monoclonal-antibodies-by-hybrid-mass-spectrometric-approaches
#9
Yang Yang, Guanbo Wang, Ting Song, Carlito B Lebrilla, Albert J R Heck
For therapeutic monoclonal antibodies (mAbs), detailed analysis of the structural integrity and heterogeneity, which results from multiple types of post-translational modifications (PTMs), is relevant to various processes, including product characterization, storage stability and quality control. Despite the recent rapid development of new bioanalytical techniques, it is still challenging to completely characterize the proteoform profile of a mAb. As a nearly indispensable tool in mAb analysis, mass spectrometry (MS) provides unique structural information at multiple levels...
February 14, 2017: MAbs
https://www.readbyqxmd.com/read/28280500/post-translational-modifications-in-regulation-of-chloroplast-function-recent-advances
#10
REVIEW
Magda Grabsztunowicz, Minna M Koskela, Paula Mulo
Post-translational modifications (PTMs) of proteins enable fast modulation of protein function in response to metabolic and environmental changes. Phosphorylation is known to play a major role in regulating distribution of light energy between the Photosystems (PS) I and II (state transitions) and in PSII repair cycle. In addition, thioredoxin-mediated redox regulation of Calvin cycle enzymes has been shown to determine the efficiency of carbon assimilation. Besides these well characterized modifications, recent methodological progress has enabled identification of numerous other types of PTMs in various plant compartments, including chloroplasts...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28278386/structural-evaluations-of-tau-protein-conformation-methodologies-and-approaches
#11
Nicole Lauren Zabik, Matthew Martin Imhof, Sanela Martic
Protein-misfolding diseases are based on a common principle of aggregation initiated by intra- and intermolecular contacts. The structural and conformational changes, induced by biochemical transformations, such as post-translational modifications (PTMs), often lead to protein unfolding and misfolding. Thus, these order-to-disorder or disorder-to-order transitions may regulate cellular function. Tau, a neuronal protein, regulates microtubule (MT) structure and overall cellular integrity. However, misfolded tau modified by PTMs results in MT destabilization, toxic tau aggregate formation, and ultimately cell death, leading to neurodegeneration...
March 9, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28276484/acetylation-and-phosphorylation-control-both-local-and-global-stability-of-the-chloroplast-f1-atp-synthase
#12
Carla Schmidt, Victoria Beilsten-Edmands, Shabaz Mohammed, Carol V Robinson
ATP synthases (ATPases) are enzymes that produce ATP and control the pH in the cell or cellular compartments. While highly conserved over different species, ATPases are structurally well-characterised but the existence and functional significance of many post-translational modifications (PTMs) is not well understood. We combined a range of mass spectrometric techniques to unravel the location and extent of PTMs in the chloroplast ATP synthase (cATPase) purified from spinach leaves. We identified multiple phosphorylation and acetylation sites and found that both modifications stabilise binding of ε and δ subunits...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28272507/scrutiny-of-mycobacterium-tuberculosis-19-kda-antigen-proteoforms-provides-new-insights-in-the-lipoglycoprotein-biogenesis-paradigm
#13
Julien Parra, Julien Marcoux, Isabelle Poncin, Stéphane Canaan, Jean Louis Herrmann, Jérôme Nigou, Odile Burlet-Schiltz, Michel Rivière
Post-translational modifications (PTMs) are essential processes conditioning the biophysical properties and biological activities of the vast majority of mature proteins. However, occurrence of several distinct PTMs on a same protein dramatically increases its molecular diversity. The comprehensive understanding of the functionalities resulting from any particular PTM association requires a highly challenging full structural description of the PTM combinations. Here, we report the in-depth exploration of the natural structural diversity of the M...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270257/new-developments-in-probing-and-targeting-protein-acylation-in-malaria-leishmaniasis-and-african-sleeping-sickness
#14
Markus Ritzefeld, Megan H Wright, Edward W Tate
Infections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases...
March 8, 2017: Parasitology
https://www.readbyqxmd.com/read/28255820/a-powerful-tool-for-assessing-distribution-and-fate-of-potentially-toxic-metals-ptms-in-soils-integration-of-laser-ablation-spectrometry-la-icp-ms-on-thin-sections-with-soil-micromorphology-and-geochemistry
#15
Fabio Scarciglia, Donatella Barca
The dynamic behavior and inherent spatial heterogeneity, at different hierarchic levels, of the soil system often make the spatial distribution of potentially toxic metals (PTMs) quite complex and difficult to assess correctly. This work demonstrates that the application of laser ablation spectrometry (LA-ICP-MS) to soil thin sections constitutes an ancillary powerful tool to well-established analytical methods for tracing the behavior and fate of potential soil contaminants at the microsite level. It allowed to discriminate the contribution of PTMs in distinct soil sub-components, such as parent rock fragments, neoformed, clay-enriched or humified matrix, and specific pedogenetic features of illuvial origin (unstained or iron-stained clay coatings) even at very low contents...
March 2, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28253954/assessment-of-posttranslational-modifications-of-atg-proteins
#16
Y Xie, R Kang, D Tang
Posttranslational modifications (PTMs) increase the functional diversity of proteins and play a key role in many cellular processes. Macroautophagy (hereafter simply referred to as autophagy) is an evolutionarily conserved, lysosome-dependent degradation pathway. This process is finely regulated by autophagy-related (ATG) genes widely conserved among eukaryotes from yeast to mammals. Various PTMs of ATG proteins such as phosphorylation, ubiquitination, and acetylation have been theorized to play a critical role in modulating autophagic processes and activity...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28248254/partial-immunoblotting-of-2d-gels-a-novel-method-to-identify-post-translationally-modified-proteins-exemplified-for-the-myelin-acetylome
#17
Kathrin Kusch, Marina Uecker, Thomas Liepold, Wiebke Möbius, Christian Hoffmann, Heinz Neumann, Hauke B Werner, Olaf Jahn
Post-translational modifications (PTMs) play a key role in regulating protein function, yet their identification is technically demanding. Here, we present a straightforward workflow to systematically identify post-translationally modified proteins based on two-dimensional gel electrophoresis. Upon colloidal Coomassie staining the proteins are partially transferred, and the investigated PTMs are immunodetected. This strategy allows tracking back the immunopositive antigens to the corresponding spots on the original gel, from which they are excised and mass spectrometrically identified...
January 12, 2017: Proteomes
https://www.readbyqxmd.com/read/28248251/impact-of-post-translational-modifications-of-crop-proteins-under-abiotic-stress
#18
REVIEW
Akiko Hashiguchi, Setsuko Komatsu
The efficiency of stress-induced adaptive responses of plants depends on intricate coordination of multiple signal transduction pathways that act coordinately or, in some cases, antagonistically. Protein post-translational modifications (PTMs) can regulate protein activity and localization as well as protein-protein interactions in numerous cellular processes, thus leading to elaborate regulation of plant responses to various external stimuli. Understanding responses of crop plants under field conditions is crucial to design novel stress-tolerant cultivars that maintain robust homeostasis even under extreme conditions...
December 21, 2016: Proteomes
https://www.readbyqxmd.com/read/28248235/extraction-and-characterization-of-extracellular-proteins-and-their-post-translational-modifications-from-arabidopsis-thaliana-suspension-cell-cultures-and-seedlings-a-critical-review
#19
REVIEW
Mina Ghahremani, Kyla A Stigter, William Plaxton
Proteins secreted by plant cells into the extracellular space, consisting of the cell wall, apoplastic fluid, and rhizosphere, play crucial roles during development, nutrient acquisition, and stress acclimation. However, isolating the full range of secreted proteins has proven difficult, and new strategies are constantly evolving to increase the number of proteins that can be detected and identified. In addition, the dynamic nature of the extracellular proteome presents the further challenge of identifying and characterizing the post-translational modifications (PTMs) of secreted proteins, particularly glycosylation and phosphorylation...
September 1, 2016: Proteomes
https://www.readbyqxmd.com/read/28248229/mitochondrial-proteome-studies-in-seeds-during-germination
#20
REVIEW
Malgorzata Czarna, Marta Kolodziejczak, Hanna Janska
Seed germination is considered to be one of the most critical phases in the plant life cycle, establishing the next generation of a plant species. It is an energy-demanding process that requires functioning mitochondria. One of the earliest events of seed germination is progressive development of structurally simple and metabolically quiescent promitochondria into fully active and cristae-containing mitochondria, known as mitochondrial biogenesis. This is a complex and tightly regulated process, which is accompanied by sequential and dynamic gene expression, protein synthesis, and post-translational modifications...
June 21, 2016: Proteomes
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