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https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#1
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28642327/declining-histone-acetyltransferase-gcn5-represses-bmsc-mediated-angiogenesis-during-osteoporosis
#2
Huan Jing, Li Liao, Xiaoxia Su, Yi Shuai, Xinjing Zhang, Zhihong Deng, Yan Jin
Angiogenesis is disrupted in age-related and postmenopausal osteoporosis. However, the mechanisms of the disorder remain elusive. We confirmed in this study that, in accordance with the decrease of H-type vessels, the proangiogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) declined during osteoporosis. Screening of the histone acetyltransferase family revealed that GCN5 decreased in BMSCs derived from osteoporotic femur. Further analysis identified that GCN5 plays important roles in regulating the proangiogenic potential of BMSCs...
June 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28594263/phototrophy-and-starvation-based-induction-of-autophagy-upon-removal-of-gcn5-catalyzed-acetylation-of-atg7-in-magnaporthe-oryzae
#3
Shulin Zhang, Meiling Liang, Naweed Naqvi, Chaoxiang Lin, Wanqiang Qian, Lian-Hui Zhang, Yi Zhen Deng
Magnaporthe oryzae, the ascomycete fungus that causes rice blast disease, initiates conidiation in response to light when grown on Prune-Agar medium containing both carbon and nitrogen sources. Macroautophagy/autophagy was shown to be essential for M. oryzae conidiation and induced specifically upon exposure to light but is undetectable in the dark. Therefore, it is inferred that autophagy is naturally induced by light, rather than by starvation during M. oryzae conidiation. However, the signaling pathway(s) involved in such phototropic induction of autophagy remains unknown...
June 8, 2017: Autophagy
https://www.readbyqxmd.com/read/28559487/a-toxin-involved-in-salmonella-persistence-regulates-its-activity-by-acetylating-its-cognate-antitoxin-a-modification-reversed-by-cobb-sirtuin-deacetylase
#4
Chelsey M VanDrisse, Anastacia R Parks, Jorge C Escalante-Semerena
Bacterial toxin-antitoxin systems trigger the onset of a persister state by inhibiting essential cellular processes. The TacT toxin of Salmonella enterica is known to induce a persister state in macrophages through the acetylation of aminoacyl-tRNAs. Here, we show that the TacT toxin and the TacA antitoxin work as a complex that modulates TacT activity via the acetylation state of TacA. TacT acetylates TacA at residue K44, a modification that is removed by the NAD(+)-dependent CobB sirtuin deacetylase. TacA acetylation increases the activity of TacT, downregulating protein synthesis...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28559430/acetylation-of-cavin-1-promotes-lipolysis-in-white-adipose-tissue
#5
Shui-Rong Zhou, Liang Guo, Xu Wang, Yang Liu, Wan-Qiu Peng, Yuan Liu, Xiang-Bo Wei, Xin Dou, Meng Ding, Qun-Ying Lei, Shu-Wen Qian, Xi Li, Qi-Qun Tang
White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which was under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1...
May 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28541373/the-histone-acetylation-mediated-by-gcn5-regulates-the-hoxc11-gene-expression-in-mefs
#6
Ji Hoon Oh, Ji-Yeon Lee, Kyoung-Ah Kong, Jie Min Kim, Myoung Hee Kim
Hox genes are responsible for encoding transcription factors that are essential for anterior-posterior body patterning at early stages of embryogenesis. However, detailed mechanisms of Hox genes are yet to be defined. Protein kinase B alpha (Akt1) was previously identified as a possible upstream regulator of Hox genes. Furthermore, the Hoxc11 gene has been upregulated in Akt1 null (Akt1-/-) mouse embryonic fibroblasts (MEFs), while repressed in wild-type MEFs. In this study, we propose to investigate the role of Gcn5, a histone acetyltransferase, in the regulation of Hoxc11 expression in MEFs...
May 24, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28539332/identification-and-characterization-of-two-types-of-amino-acid-regulated-acetyltransferases-in-actinobacteria
#7
Yu-Xing Lu, Xin-Xin Liu, Wei-Bin Liu, Bang-Ce Ye
One hundred and fifty GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N- acetyltransferase (GNAT) domain organization have been identified in actinobacteria. The ACT domain is fused to the GNAT domain, conferring amino acid-induced allosteric regulation to these protein acetyltransferases (AAPatA). Members of the AAPatA family share similar secondary structure and are divided into two groups based on the allosteric ligands of the ACT domain: the asparagine-activated PatA and the cysteine-activated PatA...
May 24, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28487409/rice-homeodomain-protein-wox11-recruits-a-histone-acetyltransferase-complex-to-establish-programs-of-cell-proliferation-of-crown-root-meristem
#8
Shaoli Zhou, Wei Jiang, Fei Long, Saifeng Cheng, Wenjing Yang, Yu Zhao, Dao-Xiu Zhou
Shoot-borne crown roots are the major root system in cereals. Previous work has shown that the Wuschel-related homeobox gene WOX11 is necessary and sufficient to promote rice (Oryza sativa) crown root emergence and elongation. Here, we show that WOX11 recruits the ADA2-GCN5 histone acetyltransferase module to activate downstream target genes in crown root meristem. Rice ADA2 and GCN5 genes are highly expressed in root meristem and are shown to be essential for cell division and growth. WOX11 and ADA2-GCN5 commonly target and regulate a set of root-specific genes involved in energy metabolism, cell wall biosynthesis, and hormone response, some of which are known to be important for root development...
May 2017: Plant Cell
https://www.readbyqxmd.com/read/28486510/acetyl-group-coordinated-progression-through-the-catalytic-cycle-of-an-arylalkylamine-n-acetyltransferase
#9
Adam A Aboalroub, Ashleigh B Bachman, Ziming Zhang, Dimitra Keramisanou, David J Merkler, Ioannis Gelis
The transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in driving the ordered formation of binary and ternary complexes remains elusive. Herein, we show that CoA and acetyl-CoA alter the conformation of the substrate binding site of an arylalkylamine N-acetyltransferase (AANAT) to facilitate interaction with acceptor substrates...
2017: PloS One
https://www.readbyqxmd.com/read/28447752/islet-1-induces-the-differentiation-of-mesenchymal-stem-cells-into-cardiomyocyte-like-cells-through-the-regulation-of-gcn5-and-dnmt-1
#10
Qin Yi, Hao Xu, Ke Yang, Yue Wang, Bin Tan, Jie Tian, Jing Zhu
Previous studies from this group demonstrated that insulin gene enhancer binding protein ISL-1 (Islet-1) specifically induces the differentiation of mesenchymal stem cells (MSCs) into cardiomyocyte‑like cells through histone acetylation. However, the underlying mechanisms remain unclear. In the present study, the role of the histone acetylation and DNA methylation on the regulatory mechanism of the Islet‑1 was further investigated by methylation‑specific polymerase chain reaction (PCR), chromatin immunoprecipitation quantitative PCR and western blot analysis...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28445968/usp22-knockdown-enhanced-chemosensitivity-of-hepatocellular-carcinoma-cells-to-5-fu-by-up-regulation-of-smad4-and-suppression-of-akt
#11
Jing Zhang, Nan Luo, Yu Tian, Jiazhi Li, Xiaozhou Yang, Huimin Yin, Congshu Xiao, Jie Sheng, Yang Li, Bo Tang, Rongkuan Li
USP22, a member of the deubiquitinases (DUBs) family, is known to be a key subunit of the human Spt-Ada-Gcn5 acetyltransferase (hSAGA) transcriptional cofactor complex. Within hSAGA, USP22 removes ubiquitin from histone proteins, thus regulating the transcription and expression of downstream genes. USP22 plays important roles in many cancers; however, its effect and the mechanism underlying HCC chemoresistance remain unclear. In the present study, we found that USP22 was highly expressed in chemoresistant HCC tissues and cells and was correlated with the prognosis of HCC patients who received chemotherapy...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439035/the-regulation-function-and-detection-of-protein-acetylation-in-bacteria
#12
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
https://www.readbyqxmd.com/read/28426192/profiling-cellular-substrates-of-lysine-acetyltransferases-gcn5-and-p300-with-orthogonal-labeling-and-click-chemistry
#13
Zhen Han, Chau-Wen Chou, Xiangkun Yang, Michael G Bartlett, Y George Zheng
p300 and GCN5 are two representative lysine acetyltransferases (KATs) in mammalian cells. It was recently reported that they possess multiple acyltransferase activities including acetylation, propionylation, and butyrylation of the ε-amino group of lysine residues of histones and non-histone protein substrates. Although thousands of acetylated substrates and acetylation sites have been identified by mass spectrometry-based proteomic screening, our knowledge about the causative connections between individual KAT members and their corresponding sub-acylomes remain very limited...
April 26, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28426094/sirt7-dependent-deacetylation-of-cdk9-activates-rna-polymerase-ii-transcription
#14
Maximilian F Blank, Sifan Chen, Fabian Poetz, Martina Schnölzer, Renate Voit, Ingrid Grummt
SIRT7 is an NAD+-dependent protein deacetylase that regulates cell growth and proliferation. Previous studies have shown that SIRT7 is required for RNA polymerase I (Pol I) transcription and pre-rRNA processing. Here, we took a proteomic approach to identify novel molecular targets and characterize the role of SIRT7 in non-nucleolar processes. We show that SIRT7 interacts with numerous proteins involved in transcriptional regulation and RNA metabolism, the majority of interactions requiring ongoing transcription...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28424240/the-histone-acetyltransferase-gcn5-positively-regulates-t-cell-activation
#15
Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang
Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28412741/opposite-effects-of-gcn5-and-pcaf-knockdowns-on-the-alternative-mechanism-of-telomere-maintenance
#16
Maya Jeitany, Dalal Bakhos-Douaihy, David C Silvestre, Jose R Pineda, Nicolas Ugolin, Angela Moussa, Laurent R Gauthier, Didier Busso, Marie-Pierre Junier, Hervé Chneiweiss, Sylvie Chevillard, Chantal Desmaze, François D Boussin
Cancer cells can use a telomerase-independent mechanism, known as alternative lengthening of telomeres (ALT), to elongate their telomeres. General control non-derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF) are two homologous acetyltransferases that are mutually exclusive subunits in SAGA-like complexes. Here, we reveal that down regulation of GCN5 and PCAF had differential effects on some phenotypic characteristics of ALT cells. Our results suggest that GCN5 is present at telomeres and opposes telomere recombination, in contrast to PCAF that may indirectly favour them in ALT cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412357/crystal-structure-of-pseudomonas-aeruginosa-n-acetyltransferase-pa4534
#17
Sungwook Shin, Jungwoo Choe
The GCN5-related N-acetyltransferase (GNAT) superfamily includes a large and diverse group of enzymes that catalyzes the transfer of an acetyl group from acetyl coenzyme A (Ac-CoA) to the amine group of a substrate. Substrates include protein N-terminus, lysine of histone tails, and other small molecules such as aminoglycoside, serotonin, and glucose-6-phosphate. GNAT superfamily of proteins is involved in many physiologically important reactions in eukaryotes and prokaryotes. However, functions of many GNATs remain unknown and PA4534 is one of those uncharacterized GNAT proteins from Pseudomonas aeruginosa...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28401181/kat2-mediated-plk4-acetylation-contributes-to-genomic-stability-by-preserving-centrosome-number
#18
Marjorie Fournier, László Tora
We have recently identified the first human lysine (K) acetyltransferase 2A and 2B (called KAT2A/2B; known also as GCN5/PCAF, respectively)-dependent acetylome and revealed a mechanism by which KAT2A/2B-mediated acetylation of serine/threonine polo-like kinase 4 (PLK4) maintains correct centrosome number in human cells, therefore contributing to the maintenance of genome stability.(1).
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28400515/saga-complex-mediates-the-transcriptional-up-regulation-of-antiviral-rna-silencing
#19
Ida Bagus Andika, Atif Jamal, Hideki Kondo, Nobuhiro Suzuki
Pathogen recognition and transcriptional activation of defense-related genes are crucial steps in cellular defense responses. RNA silencing (RNAi) functions as an antiviral defense in eukaryotic organisms. Several RNAi-related genes are known to be transcriptionally up-regulated upon virus infection in some host organisms, but little is known about their induction mechanism. A phytopathogenic ascomycete, Cryphonectria parasitica (chestnut blight fungus), provides a particularly advantageous system to study RNAi activation, because its infection by certain RNA viruses induces the transcription of dicer-like 2 (dcl2) and argonaute-like 2 (agl2), two major RNAi players...
April 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28334815/gcn5-mediated-rph1-acetylation-regulates-its-autophagic-degradation-under-dna-damage-stress
#20
Feng Li, Liang-De Zheng, Xin Chen, Xiaolu Zhao, Scott D Briggs, Hai-Ning Du
Histone modifiers regulate proper cellular activities in response to various environmental stress by modulating gene expression. In budding yeast, Rph1 transcriptionally represses many DNA damage or autophagy-related gene expression. However, little is known how Rph1 is regulated during these stress conditions. Here, we report that Rph1 is degraded upon DNA damage stress conditions. Notably, this degradation occurs via the autophagy pathway rather than through 26S proteasome proteolysis. Deletion of ATG genes or inhibition of vacuole protease activity compromises Rph1 turnover...
May 19, 2017: Nucleic Acids Research
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