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Dai Hatakeyama, Masaki Shoji, Seiya Yamayoshi, Rina Yoh, Naho Ohmi, Shiori Takenaka, Ayaka Saitoh, Yumie Arakaki, Aki Masuda, Tsugunori Komatsu, Rina Nagano, Masahiro Nakano, Takeshi Noda, Yoshihiro Kawaoka, Takashi Kuzuhara
Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the CREB-binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities...
March 19, 2018: Journal of Biological Chemistry
Laurie Galvan, Laetitia Francelle, Marie-Claude Gaillard, Lucie de Longprez, Maria-Angeles Carrillo-de Sauvage, Géraldine Liot, Karine Cambon, Lev Stimmer, Sophie Luccantoni, Julien Flament, Julien Valette, Michel de Chaldée, Gwenaelle Auregan, Martine Guillermier, Charlène Joséphine, Fanny Petit, Caroline Jan, Margot Jarrige, Noëlle Dufour, Gilles Bonvento, Sandrine Humbert, Frédéric Saudou, Philippe Hantraye, Karine Merienne, Alexis-Pierre Bemelmans, Anselme L Perrier, Nicole Déglon, Emmanuel Brouillet
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (doublecortin like kinase 3), which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington's disease. Recent data obtained in studies related to cancer suggest DCLK3 could have an anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington's disease may render striatal neurons more susceptible to mutant huntingtin (mHtt)...
March 9, 2018: Brain: a Journal of Neurology
Marta Cova, Borja López-Gutiérrez, Sara Artigas-Jerónimo, Aida González-Díaz, Giulia Bandini, Steven Maere, Lorenzo Carretero-Paulet, Luis Izquierdo
Apicomplexa form a phylum of obligate parasitic protozoa of great clinical and veterinary importance. These parasites synthesize glycoconjugates for their survival and infectivity, but the enzymatic steps required to generate the glycosylation precursors are not completely characterized. In particular, glucosamine-phosphate N-acetyltransferase (GNA1) activity, needed to produce the essential UDP-N-acetylglucosamine (UDP-GlcNAc) donor, has not been identified in any Apicomplexa. We scanned the genomes of Plasmodium falciparum and representatives from six additional main lineages of the phylum for proteins containing the Gcn5-related N-acetyltransferase (GNAT) domain...
March 5, 2018: Scientific Reports
Tianya Wang, Jiewen Xing, Xinye Liu, Yingyin Yao, Zhaorong Hu, Huiru Peng, Mingming Xin, Dao-Xiu Zhou, Yirong Zhang, Zhongfu Ni
Cuticular wax is a major composition of plant surface cuticle, which exerts crucial functions in optimizing plant growth. Histone acetylation regulates gene expressions in diverse biological processes, but its role in cuticular wax synthesis is not well understood. Here we observed that mutations of the Arabidopsis histone acetyltransferase GENERAL CONTROL NON-REPRESSED PROTEIN5 (GCN5) impaired stem cuticular wax accumulation. Three target genes of GCN5, ECERIFERUM3 (CER3), CER26 and CER1-LIKE1 (CER1-L1), were identified by RNA-Seq and ChIP assays...
March 1, 2018: Journal of Experimental Botany
Iain Scott, Lingdi Wang, Kaiyuan Wu, Dharendra Thapa, Michael N Sack
General control of amino acid synthesis 5 (GCN5) like-1 (GCN5L1) was identified as a novel gene with sequence homology to the histone acetyltransferase Gcn5. Subsequent protein-interaction studies identified GCN5L1 as a subunit of the multiprotein lysosome biogenesis complex, resulting in an alternative designation as biogenesis of lysosome-related organelle complex 1 subunit 1 (BLOS1 or BLOC1S1). Despite the distinct nomenclatures, GCN5L1/BLOS1 has been shown to play crucial roles in mitochondria, endosomes, lysosomes, and synaptic vesicle precursors (SVPs)...
February 21, 2018: Trends in Cell Biology
Jianbin Lai, Jieming Jiang, Qian Wu, Ning Mao, Danlu Han, Huan Hu, Chengwei Yang
DNA damage occurs in all cells and can hinder chromosome stability and cell viability. Structural Maintenance of Chromosomes 5/6 (SMC5/6) is a protein complex that functions as an evolutionarily conserved chromosomal ATPase critical for repairing DNA double-strand breaks (DSBs). However, the mechanisms regulating this complex in plants are poorly understood. Here, we identified the transcriptional coactivator ALTERATION/DEFICIENCY IN ACTIVATION 2B (ADA2b) as an interactor of SMC5 in Arabidopsis thaliana. ADA2b is a conserved component of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, which functions in transcriptional regulation...
February 20, 2018: Plant Physiology
Hongliang Qian, Qingqing Yao, Cui Tai, Zixin Deng, Jianhua Gan, Hong-Yu Ou
A type II toxin-antitoxin (TA) system, in which the toxin contains a Gcn5-related N-acetyltransferase (GNAT) domain, has been characterized recently. GNAT toxin acetylates aminoacyl-tRNA and blocks protein translation. It is abolished by the cognate antitoxin that contains the ribbon-helix-helix (RHH) domain. Here, we present an experimental demonstration of the interaction of the GNAT-RHH complex with TA promoter DNA. First, the GNAT-RHH TA locus kacAT was found in Klebsiella pneumoniae HS11286, a strain resistant to multiple antibiotics...
February 20, 2018: Molecular Microbiology
Xiao Fu, Chunyan Zhang, Hao Meng, Kai Zhang, Lei Shi, Cheng Cao, Ye Wang, Chao Su, Lingbiao Xin, Yuanyuan Ren, Wei Zhang, Xiaoming Sun, Lin Ge, Olli Silvennoinen, Zhi Yao, Xi Yang, Jie Yang
Herein, Tudor-SN was identified as a DNA damage response (DDR)-related protein that plays important roles in the early stage of DDR. X-ray or laser irradiation could evoke the accumulation of Tudor-SN to DNA damage sites in a poly(ADP-ribosyl)ation-dependent manner via interaction with PARP-1. Additionally, we illustrated that the SN domain of Tudor-SN mediated the association of these two proteins. The accumulated Tudor-SN further recruited SMARCA5 (ATP-dependent chromatin remodeller) and GCN5 (histone acetyltransferase) to DNA damage sites, resulting in chromatin relaxation, and consequently activating the ATM kinase and downstream DNA repair signalling pathways to promote cell survival...
February 19, 2018: Cell Death and Differentiation
Tyler J Lahusen, Seung-Jin Kim, Kai Miao, Zebin Huang, Xiaoling Xu, Chu-Xia Deng
Breast cancer associated gene 1 (BRCA1) function has been shown to be regulated by phosphorylation but the role of acetylation has not been determined. Therefore, we tested whether BRCA1 can be acetylated by the acetyltransferases P300/CBP-associated factor (pCAF), GCN5, and p300. p300 exhibited the highest level of BRCA1 acetylation; however, there was also a decrease in the total level of BRCA1. Therefore, we focused on pCAF and GCN5 because they both acetylated BRCA1 without affecting BRCA1 expression. Further analysis indicated that the acetylated form of BRCA1 is deacetylated by wild-type (WT) SIRT1, but not deacetylase mutant SIRT1, suggesting that SIRT1 is a specific deacetylase of BRCA1...
February 14, 2018: Oncogene
Shaohua Qi, Lingaonan He, Qin Zhang, Qing Dong, Yajun Wang, Qiuying Yang, Chaoguang Tian, Qun He, Ying Wang
Catalase is an important enzyme found in nearly all aerobic organisms and plays an essential role in protecting cells from oxidative damage by catalyzing the degradation of hydrogen peroxide into water and oxygen. In filamentous fungus Neurospora crassa, the expression levels of catalases are rigorously regulated by morphogenetic transition during growth and development in cells. Our study revealed that catalase-3 transcription is positively regulated by histone acetyltransferase GCN5 and the cross-pathway control gene cpc-1, as the cat-3 expression level is significantly decreased in gcn5KO and cpc-1 (j-5) mutants...
February 5, 2018: Free Radical Biology & Medicine
Qing Cai, Juan-Juan Wang, Bo Fu, Sheng-Hua Ying, Ming-Guang Feng
Gcn5 is a core histone acetyltransferase that catalyzes histone H3 acetylation on N-terminal lysine residues in yeasts and was reported to catalyze H3K9/K14 acetylation required for activating asexual development in Aspergillus. Here, we report a localization of Gcn5 ortholog in the nucleus and cytoplasm of Beauveria bassiana, a fungal insect pathogen. Deletion of gcn5 led to hypoacetylated H3 at K9/14/18/27 and 97% reduction in conidiation capacity as well as severe defects in colony growth and conidial thermotolerance...
February 7, 2018: Environmental Microbiology
Huan Jing, Xiaoxia Su, Bo Gao, Yi Shuai, Ji Chen, Zhihong Deng, Li Liao, Yan Jin
Disrupted Wnt signaling in osteoblastic-lineage cells leads to bone formation defect in osteoporosis. However, the factors repressing Wnt signaling are unclear. In our study, we found that Wnt signaling was suppressed persistently in bone marrow-derived mesenchymal stem cells (BMSCs) during osteoporosis. Accordingly, histone acetylation levels on Wnt genes (Wnt1, Wnt6, Wnt10a, and Wnt10b) were declined in BMSCs from OVX mice. By screening the family of histone acetyltransferase, we identified that GCN5 expression increased during osteogenic differentiation of BMSCs, whereas decreased after osteoporosis...
February 7, 2018: Cell Death & Disease
Qian Pan, Feng-Lan Zhao, Bang-Ce Ye
Enhanced intracellular survival (Eis) proteins were found to enhance the intracellular survival of mycobacteria in macrophages by acetylating aminoglycoside antibiotics to confer resistance to these antibiotics and by acetylating DUSP16/MPK-7 to suppress host innate immune defenses. Eis homologs composing of two GCN5 N-acetyltransferase regions and a sterol carrier protein fold are found widely in gram-positive bacteria. In this study, we found that Eis proteins have an unprecedented ability to acetylate many arylalkylamines, are a novel type of arylalkylamine N-acetyltransferase AANAT (EC 2...
February 5, 2018: Scientific Reports
Stephanie W Chun, Meagan E Hinze, Meredith A Skiba, Alison R Narayan
Like many complex natural products, the intricate architecture of saxitoxin (STX) has hindered full exploration of this scaffold's utility as a tool for studying voltage-gated sodium ion channels and as a pharmaceutical agent. Established chemical strategies can provide access to the natural product; however, a chemoenzymatic route to saxitoxin that could provide expedited access to related compounds has not been devised. The first step toward realizing a chemoenzymatic approach toward this class of molecules is the elucidation of the saxitoxin biosynthetic pathway...
February 1, 2018: Journal of the American Chemical Society
M Yu Mazina, P K Derevyanko, E V Kocheryzhkina, Yu V Nikolenko, A N Krasnov, N E Vorobyeva
The objective of this study was to identify transcriptional coactivators participating in transcription elongation of the hsp70 gene induced by heat shock. We found that all investigated coactivator complexes participate in transcription of this gene, as significant level of them were present at the gene promoter in its active state. For most of the coactivators (except for p300/CBP, Set2, and Mediator complex), we also observed a considerable increase of their binding level at the coding region of the gene after activation of its transcription by heat shock...
February 2017: Genetika
Kian Ping Chan, Sheng-Hao Chao, James Chen Yong Kah
DNA conjugated gold nanoparticles (AuNPs) have been shown to enhance the translation of mRNA. However, the specific sequence on the DNA dictates the specific mRNA to be enhanced. This study describes poly(thymine) functionalized AuNPs (AuNP-p(T)DNA) that is capable of enhancing the translation of any mRNA templates that are incorporated into pcDNA6 vector with BGH polyadenylation signal (P(A)). We demonstrated this by incorporating four genes: green fluorescence protein (GFP), general control nonderepressible 5 (GCN5), cAMP responsive element binding protein 1 (CREB1) and X-box binding protein 1-spliced (XBP-1S) separately into pcDNA6 vector with BGH P(A) before their expression in HeLa lysate...
January 24, 2018: ACS Applied Materials & Interfaces
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The proto-oncogene MYC is a transcription factor over-expressed in many cancers and required for cell survival. Its function is regulated by histone acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60 complex. However, the roles of the HAT complexes during MYC function in cancer have not been well characterized. We recently showed that adenovirus E1A and its N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4 complex...
November 2017: Genes & Cancer
Shang-Jie Yu, Ya-Lin Chang, Ying-Lien Chen
Candida glabrata, the second most frequent cause of candidiasis after Candida albicans, is an emerging human fungal pathogen that is intrinsically drug tolerant. Currently, studies of C. glabrata genes involved in drug tolerance are limited. Ada2, a component serving as a transcription adaptor of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, is required for antifungal drug tolerance and virulence in C. albicans However, its roles in C. glabrata remain elusive. In this study, we found that ada2 mutants demonstrated severe growth defects at 40°C but only mild defects at 37°C or 25°C...
January 8, 2018: Antimicrobial Agents and Chemotherapy
Sameer Salunkhe, Saket V Mishra, Jyothi Nair, Samadri Ghosh, Neha Choudhary, Ekjot Kaur, Sanket Shah, Ketaki Patkar, Dev Anand, Navin Khattry, Syed K Hasan, Shilpee Dutt
Leukemia is majorly treated by topoisomerase inhibitors that induce DNA double strand breaks (DSB) resulting in cell death. Consequently, modulation of DSB repair pathway renders leukemic cells resistant to therapy. Since we do not fully understand the regulation of DSB repair acquired by resistant cells, targeting these cells has been a challenge. Here we investigated the regulation of DSB repair pathway in Early Drug Resistant Population (EDRP) and Late Drug Resistant Population (LDRP). We found that doxorubicin induced equal DSBs in parent and EDRP cells however; cell death is induced only in the parent cells...
January 3, 2018: International Journal of Cancer. Journal International du Cancer
Li Wang, Evangelia Koutelou, Calley Hirsch, Ryan McCarthy, Andria Schibler, Kevin Lin, Yue Lu, Collene Jeter, Jianjun Shen, Michelle C Barton, Sharon Y R Dent
Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF) signaling pathway in early embryoid bodies (EBs). Gcn5-/- EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage...
December 12, 2017: Stem Cell Reports
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