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Post translational modifications

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https://www.readbyqxmd.com/read/29346445/transcriptome-analysis-of-skin-fibroblasts-with-dominant-negative-col3a1-mutations-provides-molecular-insights-into-the-etiopathology-of-vascular-ehlers-danlos-syndrome
#1
Nicola Chiarelli, Giulia Carini, Nicoletta Zoppi, Marco Ritelli, Marina Colombi
Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective tissue disorder caused by mutations in the COL3A1 gene that encodes type III collagen (COLLIII), which is the major expressed collagen in blood vessels and hollow organs. The majority of disease-causing variants in COL3A1 are glycine substitutions and in-frame splice mutations in the triple helix domain that through a dominant negative effect are associated with the severe clinical spectrum potentially lethal of vEDS, characterized by fragility of soft connective tissues with arterial and organ ruptures...
2018: PloS One
https://www.readbyqxmd.com/read/29345920/acetylation-by-eis-and-deacetylation-by-rv1151c-of-mycobacterium-tuberculosis-hupb-biochemical-and-structural-insight
#2
Keith D Green, Tapan Biswas, Allan H Pang, Melisa J Willby, Matthew S Reed, Olga Stuchlik, Jan Pohl, James E Posey, Oleg V Tsodikov, Sylvie Garneau-Tsodikova
Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity and chromosome maintenance. Post-translational modifications of bacterial NAPs appear to function similarly to their better studied mammalian counterparts. The histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously observed to be acetylated by the acetyltransferase Eis, leading to genome reorganization. We report biochemical and structural aspects of acetylation of HupB by Eis. We also found that the SirT-family NAD+-dependent deacetylase Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation kinetics...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345911/role-of-glycanation-and-convertase-maturation-of-the-soluble-glypican-3-in-inhibiting-proliferation-of-hepatocellular-carcinoma-cells
#3
Ahmad Saad, Benjamin Liet, Gilles Joucla, Xavier Santarelli, Justine Charpentier, Stéphane Claverol, Christophe F Grosset, Véronique Trézéguet
Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the outer surface of the plasma membrane by a glycosyl-phosphatidylinositol anchor (GPI). It is also N-glycosylated and processed by a furine-like convertase. GPC3 has numerous biological functions. While undetectable in normal liver tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma (HCC). Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is inhibited when they express a soluble form of GPC3 after lentiviral transduction...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29343704/phosphorylation-induced-cochaperone-unfolding-promotes-kinase-recruitment-and-client-class-specific-hsp90-phosphorylation
#4
Ashleigh B Bachman, Dimitra Keramisanou, Wanping Xu, Kristin Beebe, Michael A Moses, M V Vasantha Kumar, Geoffrey Gray, Radwan Ebna Noor, Arjan van der Vaart, Len Neckers, Ioannis Gelis
During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains...
January 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29343654/intestinal-epithelial-cell-specific-deletion-of-%C3%AE-mannosidase-ii-ameliorates-experimental-colitis
#5
Koichiro Suzuki, Takahiro Yamada, Keiko Yamazaki, Masato Hirota, Narumi Ishihara, Mizuki Sakamoto, Daisuke Takahashi, Hideki Iijima, Koji Hase
Inflammatory bowel disease (IBD) is a refractory disease of the gastrointestinal tract that is believed to develop in genetically susceptible individuals. Glycosylation, a type of post-translational modification, is involved in the development of a wide range of diseases, including IBD, by modulating the function of various glycoproteins. To identify novel genes contributing to the development of IBD, we analyzed single nucleotide polymorphisms (SNPs) of glycosylation-related genes in IBD patients and identified MAN2A1, encoding alpha-mannosidase II (α-MII), as a candidate gene...
January 18, 2018: Cell Structure and Function
https://www.readbyqxmd.com/read/29343059/top-down-characterization-of-heavily-modified-histones-using-193-nm-ultraviolet-photodissociation-uvpd-mass-spectrometry
#6
Sylvester M Greer, Jennifer S Brodbelt
The characterization of protein post-translational modifications (PTMs) remains a significant challenge for traditional bottom-up proteomics methods owing to the lability of PTMs and the difficulty of mapping combinatorial patterns of PTMs based on analysis of small peptides. These shortcomings have accelerated interest in top-down MS/MS methods which focus on analysis of intact proteins. Mapping all protein PTMs simultaneously requires the ability to obtain extensive sequence coverage to allow confident localization of the modifications...
January 18, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29341488/gene-gene-interaction-between-msx1-and-tp63-in-asian-case-parent-trios-with-nonsyndromic-cleft-lip-with-or-without-cleft-palate
#7
Dongjing Liu, Holger Schwender, Mengying Wang, Hong Wang, Ping Wang, Hongping Zhu, Zhibo Zhou, Jing Li, Tao Wu, Terri H Beaty
BACKGROUND: Small ubiquitin-like modification, also known as sumoylation, is a crucial post-translational regulatory mechanisms involved in development of the lip and palate. Recent studies reported two sumoylation target genes, MSX1 and TP63, to have achieved genome-wide level significance in tests of association with nonsyndromic clefts. Here, we performed a candidate gene analysis considering gene-gene and gene-environment interaction for SUMO1, MSX1, and TP63 to further explore the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P)...
January 17, 2018: Birth Defects Research
https://www.readbyqxmd.com/read/29341427/lc-ms-based-intact-igg-and-released-glycan-analysis-for-bioprocessing-applications
#8
Tianhua Wang, Kong Meng Hoi, Henning Stöckmann, Corrine Wan, Lyn Chiin Sim, Noor Hayati Bte Kamari, Shi Jie Tay, Ce Huang Poo, Susanto Woen, Yuangsheng Yang, Peiqing Zhang, Pauline M Rudd
Robust plate based antibody glycan analysis platforms are urgently needed for biopharmaceutical development and manufacturing as well as for clinical biomarker research. A 96-well plate based workflow has been developed to analyze both intact IgG antibodies and released N-glycans using an Orbitrap Fusion Mass Spectrometer and an LC/MS method on the Waters UNIFI platform. Here we describe such a workflow including protein A purification, PNGaseF digestion, 2-AB labeling and SPE clean-up. The measured IgG glycan profile is consistent with that obtained from non-plate based method and commercial kit and has the advantage of less hands-on time...
January 17, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29339414/assembly-of-methyl-coenzyme-m-reductase-in-the-methanogenic-archaeon-methanococcus-maripaludis
#9
Zhe Lyu, Chau-Wen Chou, Hao Shi, Liangliang Wang, Robel Ghebreab, Dennis Phillips, Yajun Yan, Evert C Duin, William B Whitman
Methyl-coenzyme M reductase (MCR) is a complex enzyme that catalyzes the final step in biological methanogenesis. To better understand its assembly, the recombinant MCR from the thermophile Methanothermococcus okinawensis (rMCRok) was expressed in the mesophile Methanococcus maripaludis The rMCRok was post-translationally modified correctly and contained McrD and the unique nickel tetrapyrrole coenzyme F430 Subunits of the native M. maripaludis (MCRmar) were largely absent, suggesting that the recombinant enzyme was formed by an assembly of co-transcribed subunits...
January 16, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29339380/negative-regulation-of-the-keap1-nrf2-pathway-by-a-p62-sqstm1-splicing-variant
#10
Shun Kageyama, Tetsuya Saito, Miki Obata, Ryo-Hei Koide, Yoshinobu Ichimura, Masaaki Komatsu
A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via multiple mechanisms, including gene expression, post-translational modifications such as ubiquitination and phosphorylation, and autophagic degradation of p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl database search and subsequent biochemical analyses in mice revealed the presence of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region (KIR), which is essential for the interaction with Keap1...
January 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29338241/characterization-of-macrophage-endogenous-s-nitrosoproteome-using-a-cysteine-specific-phosphonate-adaptable-tag-in-combination-with-tio2-chromatography
#11
Maria Ibañez-Vea, Honggang Huang, Xabier Martinez de Morentin, Estela Perez, Maria Gato, Miren Zuazo, Hugo Arasanz, Joaquin Fernandez-Irigoyen, Enrique Santamaría, Gonzalo Fernandez-Hinojal, Martin R Larsen, David Escors, Grazyna Kochan
Protein S-nitrosylation is a cysteine post-translational modification mediated by nitric oxide. An increasing number of studies highlight S-nitrosylation as an important regulator of signaling involved in numerous cellular processes. Despite of the significant progress in the development of redox proteomic methods, identification and quantification of endogeneous S-nitrosylation using high-throughput mass spectrometry-based methods is a technical challenge as this modification is highly labile. To overcome this drawback most methods induce S-nitrosylation chemically in proteins using nitrosylating compounds before analysis, with the risk of introducing non-physiological S-nitrosylation...
January 17, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29337275/the-o-%C3%AE-linked-n-acetylglucosaminylation-of-the-lamin-b-receptor-and-its-impact-on-dna-binding-and-phosphorylation
#12
Caroline Smet-Nocca, Adeline Page, François-Xavier Cantrelle, Eleni Nikolakaki, Isabelle Landrieu, Thomas Giannakouros
Lamin B Receptor (LBR) is an integral protein of the interphase inner nuclear membrane that is implicated in chromatin anchorage to the nuclear envelope. Phosphorylation of a stretch of arginine-serine (RS) dipeptides in the amino-terminal nucleoplasmic domain of LBR regulates the interactions of the receptor with other nuclear proteins, DNA and RNA and thus modulates tethering of heterochromatin to the nuclear envelope. While phosphorylation has been extensively studied, very little is known about other post-translational modifications of the protein...
January 11, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29337201/on-the-glycosylation-aspects-of-biosimilarity
#13
REVIEW
László Hajba, Ákos Szekrényes, Beáta Borza, András Guttman
The recent expiration of several protein therapeutics opened the door for biosimilar development. Biosimilars are biologic medical products that are similar but not identical copies of already-authorized protein therapeutics. Critical quality attributes (CQA), such as post-translational modifications of recombinant biotherapeutics, are important for the clinical efficacy and safety of both the innovative biologics and their biosimilar counterparts. Here, we summarize biosimilarity CQAs, considering the regulatory guidelines and the statistical aspects (e...
January 11, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29336995/a-search-for-molecular-mechanisms-underlying-male-idiopathic-infertility
#14
REVIEW
An Bracke, Kris Peeters, Usha Punjabi, David Hoogewijs, Sylvia Dewilde
Infertility affects approximately 15% of the couples wanting to conceive. In 30 - 40% of the cases the aetiology of male infertility remains unknown and is called idiopathic male infertility. When assisted reproductive technologies are used to obtain pregnancy, an adequate (epi)genetic diagnosis of male infertility is of major importance to evaluate if a genetic abnormality will be transmitted to the offspring. In addition, there is need for better diagnostic seminal biomarkers to assess the success rates of these assisted reproductive technologies...
December 27, 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/29335368/in-medio-stat-virtus-unanticipated-consequences-of-telomere-dysequilibrium
#15
REVIEW
Lea Harrington, Fabio Pucci
The integrity of chromosome ends, or telomeres, depends on myriad processes that must balance the need to compact and protect the telomeric, G-rich DNA from detection as a double-stranded DNA break, and yet still permit access to enzymes that process, replicate and maintain a sufficient reserve of telomeric DNA. When unable to maintain this equilibrium, erosion of telomeres leads to perturbations at or near the telomeres themselves, including loss of binding by the telomere protective complex, shelterin, and alterations in transcription and post-translational modifications of histones...
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29331584/protein-neddylation-and-its-alterations-in-human-cancers-for-targeted-therapy
#16
REVIEW
Lisha Zhou, Wenjuan Zhang, Yi Sun, Lijun Jia
Neddylation, a post-translational modification that conjugates an ubiquitin-like protein NEDD8 to substrate proteins, is an important biochemical process that regulates protein function. The best-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family of E3 ubiquitin ligases, control many important biological processes, including tumorigenesis, through promoting ubiquitylation and subsequent degradation of a variety of key regulatory proteins...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29331577/a-novel-encystation-specific-protein-kinase-regulates-chitin-synthesis-in-entamoeba-invadens
#17
Sintu Kumar Samanta, Sneha Susan Varghese, Deepak Krishnan, Mithu Baidya, Digant Nayak, Sumanta Mukherjee, Sudip K Ghosh
Phosphorylation is an important post-translational modification of proteins and is involved in the regulation of a variety of cellular events. The proteome of Entamoeba invadens, the reptilian counterpart of Entamoeba histolytica consists of an overwhelming number of putative protein kinases, and some may have a role to play in Entamoeba encystation. In this study, we have identified a novel protein kinase named as EiCSpk (Entamoeba invadenscyst specific protein kinase) which expressed almost exclusively during encystation...
January 10, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29331071/hepatic-ppar%C3%AE-function-is-controlled-by-polyubiquitination-and-proteasome-mediated-degradation-via-the-coordinated-actions-of-paqr3-and-huwe1
#18
Zilong Zhao, Daqian Xu, Zheng Wang, Lin Wang, Ruomei Han, Zhenzhen Wang, Lujian Liao, Yan Chen
Peroxisome proliferator-activated receptor α (PPARα) is a key transcriptional factor that regulates hepatic lipid catabolism by stimulating fatty acid oxidation and ketogenesis in an adaptive response to nutrient starvation. However, how PPARα is regulated by post-translational modification is poorly understood. Here, we identified that PAQR3 promotes PPARα ubiquitination through the E3 ubiquitin ligase HUWE1, thereby negatively modulating PPARα functions both in vitro and in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid oxidation and ketogenesis upon fasting...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29330559/a-post-translational-balancing-act-the-good-and-the-bad-of-sumoylation-in-pancreatic-islets
#19
EDITORIAL
Patrick E MacDonald
Post-translational modification of proteins contributes to the control of cell function and survival. The balance of these in insulin-producing pancreatic beta cells is important for the maintenance of glucose homeostasis. Protection from the damaging effects of reactive oxygen species is required for beta cell survival, but if this happens at the expense of insulin secretory function then the ability of islets to respond to changing metabolic conditions may be compromised. In this issue of Diabetologia, He et al ( https://doi...
January 12, 2018: Diabetologia
https://www.readbyqxmd.com/read/29330049/the-histone-demethylase-phf8-promotes-adult-acute-lymphoblastic-leukemia-through-interaction-with-the-mek-erk-signaling-pathway
#20
Yue Fu, Yaling Yang, Xiaoming Wang, Xiaolin Yin, Minran Zhou, Siqi Wang, Lin Yang, Tao Huang, Man Xu, Chunyan Chen
Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo...
January 9, 2018: Biochemical and Biophysical Research Communications
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