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https://www.readbyqxmd.com/read/28431224/adp-ribosylation-goes-normal-serine-as-the-major-site-of-the-modification
#1
Qiang Liu, Bogdan I Florea, Dmitri V Filippov
Proteins containing adenosine diphosphate ribosylserine as a posttranslational modification are widespread and formed via HPF1-assisted, PARP-1-mediated PARylation as Bonfiglio et al. (2017) report in a recent issue of Molecular Cell.
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#2
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28272405/parp1-promotes-gene-expression-at-the-post-transcriptiona-level-by-modulating-the-rna-binding-protein-hur
#3
Yueshuang Ke, Yanlong Han, Xiaolan Guo, Jitao Wen, Ke Wang, Xue Jiang, Xue Tian, Xueqing Ba, Istvan Boldogh, Xianlu Zeng
Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28257697/serious-surprises-for-adp-ribosylation-specificity-hpf1-switches-parp1-specificity-to-ser-residues
#4
Anthony K L Leung
In this issue of Molecular Cell, Bonfiglio et al. (2017) demonstrate that histone PARylation factor 1 (HPF1) is required for PARP1 to attach ADP-ribose groups onto the hydroxyl oxygen of the Ser residues of target substrates, including both PARP1 itself and histones. Here, mechanisms and implications of this unexpected, O-linked ADP-ribosylation are speculated on.
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28249904/nr1d1-recruitment-to-sites-of-dna-damage-inhibits-repair-and-is-associated-with-chemosensitivity-of-breast-cancer
#5
Na-Lee Ka, Tae-Young Na, Hyelin Na, Min-Ho Lee, Han-Su Park, Sewon Hwang, Il-Yong Kim, Je Kyung Seong, Mi-Ock Lee
DNA repair capacity is critical for survival of cancer cells upon therapeutic DNA damage and thus is an important determinant of susceptibility to chemotherapy in cancer patients. In this study, we identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both non-homologous end joining and homologous recombination double strand breaks (DSB) repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28239158/synthesis-of-the-novel-parp-1-inhibitor-ag-690-11026014-and-its-protective-effects-on-angiotensin-ii-induced-mouse-cardiac-remodeling
#6
Guo-Shuai Feng, Cui-Ge Zhu, Zhuo-Ming Li, Pan-Xia Wang, Yi Huang, Min Liu, Ping He, Lan-Lan Lou, Shao-Rui Chen, Pei-Qing Liu
We previously identified AG-690/11026014 (6014) as a novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor that effectively prevented angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. In the present study, we reported a new synthesis route for 6014, and investigated its protective effects on Ang II-induced cardiac remodeling and cardiac dysfunction and the underlying mechanisms in mice. We designed a new synthesis route to obtain a sufficient quantity of 6014 for this in vivo study. C57BL/6J mice were infused with Ang II and treated with 6014 (10, 30, 90 mg·kg(-1)·d(-1), ig) for 4 weeks...
February 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28220129/no-silver-bullet-canonical-poly-adp-ribose-polymerases-parps-are-no-universal-factors-of-abiotic-and-biotic-stress-resistance-of-arabidopsis-thaliana
#7
Dagmar Rissel, Peter P Heym, Kathrin Thor, Wolfgang Brandt, Ludger A Wessjohann, Edgar Peiter
Abiotic and biotic stress can have a detrimental impact on plant growth and productivity. Hence, there is a substantial demand for key factors of stress responses to improve yield stability of crops. Members of the poly(ADP-ribose)polymerase (PARP) protein family, which post-translationally modify (PARylate) nuclear proteins, have been suggested as such universal determinants of plant stress responses. A role under abiotic stress has been inferred from studies in which a genetic or, more commonly, pharmacological inhibition of PARP activity improved the performance of stressed plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28190768/serine-adp-ribosylation-depends-on-hpf1
#8
Juan José Bonfiglio, Pietro Fontana, Qi Zhang, Thomas Colby, Ian Gibbs-Seymour, Ilian Atanassov, Edward Bartlett, Roko Zaja, Ivan Ahel, Ivan Matic
ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. However, the biochemical basis underlying this serine modification remained unknown. Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107648/parp-1-controls-the-adipogenic-transcriptional-program-by-parylating-c-ebp%C3%AE-and-modulating-its-transcriptional-activity
#9
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/28099939/type-5-phosphodiesterase-regulates-glioblastoma-multiforme-aggressiveness-and-clinical-outcome
#10
Valeriana Cesarini, Maurizio Martini, Lucia Ricci Vitiani, Giovanni Luca Gravina, Silvia Di Agostino, Grazia Graziani, Quintino Giorgio D'Alessandris, Roberto Pallini, Luigi M Larocca, Pellegrino Rossi, Emmanuele A Jannini, Susanna Dolci
Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Herein, by analyzing a cohort of 69 patients affected by glioblastoma multiforme (GBM) who underwent chemo- and radiotherapy after surgical resection of the tumor, we found that PDE5 was strongly expressed in cancer cells in about 50% of the patients. Retrospective analysis indicated that high PDE5 expression in GBM cells significantly correlated with longer overall survival of patients...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28032120/inhibition-of-poly-adp-ribosylation-fails-to-increase-axonal-regeneration-or-improve-functional-recovery-after-adult-mammalian-cns-injury
#11
Xingxing Wang, Yuichi Sekine, Alexandra B Byrne, William B J Cafferty, Marc Hammarlund, Stephen M Strittmatter
After traumatic damage of the brain or spinal cord, many surviving neurons are disconnected, and recovery of function is limited by poor axon regeneration. Recent data have suggested that poly ADP-ribosylation plays a role in limiting axonal regrowth such that inhibition of poly (ADP-ribose) polymerase (PARP) may have therapeutic efficacy for neurological recovery after trauma. Here, we tested systemic administration of the PARP inhibitor, veliparib, and showed effective suppression of PARylation in the mouse CNS...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28013023/metabolic-roles-of-poly-adp-ribose-polymerases
#12
REVIEW
András Vida, Judit Márton, Edit Mikó, Péter Bai
Poly(ADP-ribosyl)ation (PARylation) is an evolutionarily conserved reaction that had been associated with numerous cellular processes such as DNA repair, protein turnover, inflammatory regulation, aging or metabolic regulation. The metabolic regulatory tasks of poly(ADP-ribose) polymerases (PARPs) are complex, it is based on the regulation of metabolic transcription factors (e.g. SIRT1, nuclear receptors, SREBPs) and certain cellular energy sensors. PARP over-activation can cause damage to mitochondrial terminal oxidation, while the inhibition of PARP-1 or PARP-2 can induce mitochondrial oxidation by enhancing the mitotropic tone of gene transcription and signal transduction...
March 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27965086/the-effect-of-poly-adp-ribosyl-ation-inhibition-on-the-porcine-cumulus-oocyte-complex-during-in%C3%A2-vitro-maturation
#13
Duk Hyoun Kim, Hye Ran Lee, Min Gyeong Kim, Jun Sung Lee, Su Jin Jin, Hoon Taek Lee
Poly(ADP-ribosyl)ation (PARylation) plays important roles in DNA repair, apoptosis, transcriptional regulation, and cell death, and occurs via the activity of poly(ADP-ribose) polymerases (PARPs). Previous studies have shown that PARylation affects mouse and porcine pre-implantation development and participates in mechanisms of autophagy. However, there have not yet been reported the role of PARylation during in vitro maturation (IVM) of porcine oocytes. Thus, we investigated the effect of PARylation inhibition on this process; cumulus-oocyte complexes (COCs) were cultured with 3-aminobenzamide (3-ABA, PARP inhibitor) during porcine IVM...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27920426/crystal-structure-based-discovery-of-a-novel-synthesized-parp1-inhibitor-ol-1-with-apoptosis-inducing-mechanisms-in-triple-negative-breast-cancer
#14
Leilei Fu, Shuya Wang, Xuan Wang, Peiqi Wang, Yaxin Zheng, Dahong Yao, Mingrui Guo, Lan Zhang, Liang Ouyang
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzo[b,e]-oxepin compounds as PARP1 inhibitors...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908606/parp1-orchestrates-epigenetic-events-setting-up-chromatin-domains
#15
REVIEW
Fabio Ciccarone, Michele Zampieri, Paola Caiafa
Epigenetic events include reversible modifications of DNA and histone tails driving chromatin organization and thus transcription. The epigenetic regulation is a highly integrated process underlying the plasticity of the genomic information both in the context of complex physiological and pathological processes. The global regulatory aspects of epigenetic events are largely unknown. PARylation and PARP1 are recently emerging as multi-level regulatory effectors that modulate the topology of chromatin by orchestrating very different processes...
March 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27817742/parg-inhibitors-and-functional-parg-inhibition-models
#16
Yuka Sasaki, Miyuki Hozumi, Hiroaki Fujimori, Yasufumi Murakami, Fumiaki Koizumi, Kengo Inoue, Mitsuko Masutani
Poly(ADP-ribose) polymerases (PARPs) family proteins catalyze poly(ADP-ribosylation) (PARylation) by conjugating ADP-ribose residues repeatedly on amino acid residues using nicotinamide adenine dinucleotide as a substrate. The inhibitors of PARP widely block DNA repair processes and are currently examined in clinical trials of cancer therapy. Poly(ADP-ribose) glycohydrolase (PARG) is the main nuclear enzyme, which digests poly(ADP-ribose) into ADP-ribose. PARG inhibitor could also be considered as a chemotherapeutic agent for cancer, because of its involvement in DNA repair...
2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27813108/antagonistic-effect-of-n-ethylmaleimide-on-arsenic-mediated-oxidative-stress-induced-poly-adp-ribosyl-ation-and-cytotoxicity
#17
Alexander Sheng-Shin Wang, Yu-Ting Chou, Yeong-Shiau Pu
Long-term exposure to arsenic has been known to induce neoplastic initiation and progression in several organs; however, the role of arsenic (As2 O3 ) in oxidative stress-mediated DNA damage remains elusive. One of the immediate cellular responses to DNA damage is poly(ADP-ribosyl)ation (PARylation), which mediates DNA repair and enhances cell survival. In this study, we found that oxidative stress (H2 O2 )-induced PARylation was suppressed by As2 O3 exposure in different human cancer cells. Moreover, As2 O3 treatment promoted H2 O2 -induced DNA damage and apoptosis, leading to increased cell death...
November 4, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27798264/nad-repletion-improves-muscle-function-in-muscular-dystrophy-and-counters-global-parylation
#18
Dongryeol Ryu, Hongbo Zhang, Eduardo R Ropelle, Vincenzo Sorrentino, Davi A G Mázala, Laurent Mouchiroud, Philip L Marshall, Matthew D Campbell, Amir Safi Ali, Gary M Knowels, Stéphanie Bellemin, Shama R Iyer, Xu Wang, Karim Gariani, Anthony A Sauve, Carles Cantó, Kevin E Conley, Ludivine Walter, Richard M Lovering, Eva R Chin, Bernard J Jasmin, David J Marcinek, Keir J Menzies, Johan Auwerx
Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD(+)) synthesis, consistent with a potential role for the essential cofactor NAD(+) in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD(+) and are involved in pleiotropic events, including inflammation...
October 19, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27797852/parylation-of-the-forkhead-associated-domain-protein-dawdle-regulates-plant-immunity
#19
Baomin Feng, Shisong Ma, Sixue Chen, Ning Zhu, Shuxin Zhang, Bin Yu, Yu Yu, Brandon Le, Xuemei Chen, Savithramma P Dinesh-Kumar, Libo Shan, Ping He
Protein poly(ADP-ribosyl)ation (PARylation) primarily catalyzed by poly(ADP-ribose) polymerases (PARPs) plays a crucial role in controlling various cellular responses. However, PARylation targets and their functions remain largely elusive. Here, we deployed an Arabidopsis protein microarray coupled with in vitro PARylation assays to globally identify PARylation targets in plants. Consistent with the essential role of PARylation in plant immunity, the forkhead-associated (FHA) domain protein DAWDLE (DDL), one of PARP2 targets, positively regulates plant defense to both adapted and non-adapted pathogens...
December 2016: EMBO Reports
https://www.readbyqxmd.com/read/27793508/dna-maintenance-following-bleomycin-induced-strand-breaks-does-not-require-poly-adp-ribosyl-ation-activation-in-drosophila-s2-cells
#20
Layal Ishak, Amandine Moretton, Isabelle Garreau-Balandier, Mathilde Lefebvre, Serge Alziari, Philippe Lachaume, Frédéric Morel, Géraldine Farge, Patrick Vernet, Pascal Dubessay
BACKGROUND: Poly-ADP ribosylation (PARylation) is a post translational modification, catalyzed by Poly(ADP-ribose)polymerase (PARP) family. In Drosophila, PARP-I (human PARP-1 ortholog) is considered to be the only enzymatically active isoform. PARylation is involved in various cellular processes such as DNA repair in case of base excision and strand-breaks. OBSERVATIONS: Strand-breaks (SSB and DSB) are detrimental to cell viability and, in Drosophila, that has a unique PARP family organization, little is known on PARP involvement in the control of strand-breaks repair process...
October 21, 2016: DNA Repair
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