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https://www.readbyqxmd.com/read/27910960/unc-5-homolog-b-unc5b-is-one-of-the-key-downstream-targets-of-n-%C3%AE-acetyltransferase-10-naa10
#1
Huiyu Xu, Yong Han, Bing Liu, Rong Li
N-α-acetyltransferase 10 (Naa10) displays alpha (N-terminal) acetyltransferase activity. It functions as a major modulator of cell growth and differentiation. Until now, a few downstream targets were found, but no studies have concerned about which gene is the early event of Naa10 downstream target. As we know, the earlier events may play more significant role in Naa10 pathway. Through construction of Naa10 stably knocked down H1299 cell line, we discovered cell morphological changes induced by Naa10. Moreover, potential function of Naa10 in cell morphogenesis was also indicated using cDNA microarray analysis of the Naa10 stably knock-down cell line...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27668839/proteomic-and-genomic-characterization-of-a-yeast-model-for-ogden-syndrome
#2
Max J Dörfel, Han Fang, Jonathan Crain, Michael Klingener, Jake Weiser, Gholson J Lyon
Naa10 is an N(α) -terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the α-amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40-50% of the human proteome is acetylated by Naa10, rendering this an enzyme one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harbouring a c.109 T > C (p.Ser37Pro) variant in NAA10. In the present study we performed in-depth characterization of a yeast model of Ogden syndrome...
September 26, 2016: Yeast
https://www.readbyqxmd.com/read/27610925/nata-is-required-for-suspensor-development-in-arabidopsis
#3
Jinlin Feng, Ligeng Ma
Suspensor development is essential for early embryogenesis. The filamentous suspensor plays vital roles in supporting the embryo proper and in exchanging nutrients and information between the embryo proper and embryo sac. In addition, at the globular stage, the uppermost suspensor cell differentiates into the hypophysis, which generates the progenitors of the quiescent center and columella stem cells. In naa10 and naa15 mutant plants, suspensor cell identity was found to be abnormal and embryo development was disturbed, leading to embryonic lethality...
September 9, 2016: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/27484799/human-naa50-protein-displays-broad-substrate-specificity-for-amino-terminal-acetylation-detailed-structural-and-biochemical-analysis-using-tetrapeptide-library
#4
Ravikumar Reddi, Venkateshwarlu Saddanapu, Dinesh Kumar Chinthapalli, Priyanka Sankoju, Prabhakar Sripadi, Anthony Addlagatta
Amino-terminal acetylation is a critical co-translational modification of the newly synthesized proteins in a eukaryotic cell carried out by six amino-terminal acetyltransferases (NATs). All NATs contain at least one catalytic subunit, and some contain one or two additional auxiliary subunits. For example, NatE is a complex of Naa10, Naa50, and Naa15 (auxiliary). In the present study, the crystal structure of human Naa50 suggested the presence of CoA and acetylated tetrapeptide (AcMMXX) that have co-purified with the protein...
September 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27385766/protein-n-terminal-acetylation-is-required-for-embryogenesis-in-arabidopsis
#5
Jinlin Feng, Ruiqi Li, Junya Yu, Shuangshuang Ma, Chunyan Wu, Yan Li, Ying Cao, Ligeng Ma
Early embryonic development generates precursors of all major cell types in Arabidopsis. Among these precursors, the hypophysis divides asymmetrically to form the progenitors of the quiescent center and columella stem cells. A great deal has been learnt about the mechanisms that control the asymmetric division of the hypophysis and embryogenesis at the transcriptional level; however, no evidence of regulation at the co- or post-translational level has been reported. Here, we show that mutation of the catalytic subunit (Naa10) or auxiliary subunit (Naa15) of NatA, an N-terminal acetyltransferase that catalyzes protein N-terminal acetylation, produces an embryo-lethal phenotype...
August 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27320834/crystal-structure-of-the-golgi-associated-human-n%C3%AE-acetyltransferase-60-reveals-the-molecular-determinants-for-substrate-specific-acetylation
#6
Svein Isungset Støve, Robert S Magin, Håvard Foyn, Bengt Erik Haug, Ronen Marmorstein, Thomas Arnesen
N-Terminal acetylation is a common and important protein modification catalyzed by N-terminal acetyltransferases (NATs). Six human NATs (NatA-NatF) contain one catalytic subunit each, Naa10 to Naa60, respectively. In contrast to the ribosome-associated NatA to NatE, NatF/Naa60 specifically associates with Golgi membranes and acetylates transmembrane proteins. To gain insight into the molecular basis for the function of Naa60, we developed an Naa60 bisubstrate CoA-peptide conjugate inhibitor, determined its X-ray structure when bound to CoA and inhibitor, and carried out biochemical experiments...
July 6, 2016: Structure
https://www.readbyqxmd.com/read/27094817/expanding-the-phenotype-associated-with-naa10-related-n-terminal-acetylation-deficiency
#7
Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas AhMew, Charlotte de Bie, Paula Goldenberg, Bertrand Isidor, Boris Keren, Bruno Leheup, Laetitia Lampert, Cyril Mignot, Kamer Tezcan, Grazia M S Mancini, Caroline Nava, Melissa Wasserstein, Ange-Line Bruel, Julien Thevenon, Alice Masurel, Yannis Duffourd, Paul Kuentz, Frédéric Huet, Jean-Baptiste Rivière, Marjon van Slegtenhorst, Laurence Faivre, Amélie Piton, André Reis, Thomas Arnesen, Christel Thauvin-Robinet, Christiane Zweier
N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated...
August 2016: Human Mutation
https://www.readbyqxmd.com/read/26755727/the-n-terminal-acetyltransferase-naa10-ard1-does-not-acetylate-lysine-residues
#8
Robert S Magin, Zachary M March, Ronen Marmorstein
The N-terminal acetyltransferase NatA is a heterodimeric complex consisting of a catalytic subunit (Naa10/ARD1) and an auxiliary subunit (Naa15). NatA co-translationally acetylates the N termini of a wide variety of nascent polypeptides. In addition, Naa10 can act independently to posttranslationally acetylate a distinct set of substrates, notably actin. Recent structural studies of Naa10 have also revealed the molecular basis for N-terminal acetylation specificity. Surprisingly, recent reports claim that Naa10 may also acetylate lysine residues of diverse targets, including methionine sulfoxide reductase A, myosin light chain kinase, and Runt-related transcription factor 2...
March 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26646451/microrna-342-5p-and-mir-608-inhibit-colon-cancer-tumorigenesis-by-targeting-naa10
#9
Hongju Yang, Qian Li, Jie Niu, Bai Li, Dejun Jiang, Zhihua Wan, Qingmei Yang, Fei Jiang, Ping Wei, Song Bai
miRNAs have been shown to play pivotal roles in the establishment and progression of colon cancer, but their underlying mechanisms are not fully understood. N-acetyltransferase NAA10 participates in many cellular processes, including tumorigenesis. Here we showed that miR-342-5p and miR-608 suppressed the tumorigenesis of colon cancer cells in vitro and in vivo by targeting NAA10 mRNA for degradation. Overexpression of miR-342-5p or miR-608 decreased NAA10 mRNA and protein levels and thereby suppressed cell proliferation, migration, and cell-cycle progression, as well as promoted apoptosis in SW480 and SW620 cells...
January 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26522270/naa10-mutation-causing-a-novel-intellectual-disability-syndrome-with-long-qt-due-to-n-terminal-acetyltransferase-impairment
#10
Jillian P Casey, Svein I Støve, Catherine McGorrian, Joseph Galvin, Marina Blenski, Aimee Dunne, Sean Ennis, Francesca Brett, Mary D King, Thomas Arnesen, Sally Ann Lynch
We report two brothers from a non-consanguineous Irish family presenting with a novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has a milder phenotype including long QT. X-linked inheritance was suspected. Whole exome sequencing identified a novel missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of the family's disorder. Sanger sequencing confirmed that the mutation arose de novo in the carrier mother. NAA10 encodes the catalytic subunit of the major human N-terminal acetylation complex NatA...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26431279/naa10-in-development-and-disease
#11
EDITORIAL
Line M Myklebust, Svein I Støve, Thomas Arnesen
No abstract text is available yet for this article.
October 27, 2015: Oncotarget
https://www.readbyqxmd.com/read/26251455/the-n-terminal-acetyltransferase-naa10-is-essential-for-zebrafish-development
#12
Rasmus Ree, Line M Myklebust, Puja Thiel, Håvard Foyn, Kari E Fladmark, Thomas Arnesen
N-terminal acetylation, catalysed by N-terminal acetyltransferases (NATs), is among the most common protein modifications in eukaryotes and involves the transfer of an acetyl group from acetyl-CoA to the α-amino group of the first amino acid. Functions of N-terminal acetylation include protein degradation and sub-cellular targeting. Recent findings in humans indicate that a dysfunctional Nα-acetyltransferase (Naa) 10, the catalytic subunit of NatA, the major NAT, is associated with lethality during infancy...
2015: Bioscience Reports
https://www.readbyqxmd.com/read/25987439/the-biological-functions-of-naa10-from-amino-terminal-acetylation-to-human-disease
#13
REVIEW
Max J Dörfel, Gholson J Lyon
N-terminal acetylation (NTA) is one of the most abundant protein modifications known, and the N-terminal acetyltransferase (NAT) machinery is conserved throughout all Eukarya. Over the past 50 years, the function of NTA has begun to be slowly elucidated, and this includes the modulation of protein-protein interaction, protein-stability, protein function, and protein targeting to specific cellular compartments. Many of these functions have been studied in the context of Naa10/NatA; however, we are only starting to really understand the full complexity of this picture...
August 10, 2015: Gene
https://www.readbyqxmd.com/read/25489052/biochemical-and-cellular-analysis-of-ogden-syndrome-reveals-downstream-nt-acetylation-defects
#14
Line M Myklebust, Petra Van Damme, Svein I Støve, Max J Dörfel, Angèle Abboud, Thomas V Kalvik, Cedric Grauffel, Veronique Jonckheere, Yiyang Wu, Jeffrey Swensen, Hanna Kaasa, Glen Liszczak, Ronen Marmorstein, Nathalie Reuter, Gholson J Lyon, Kris Gevaert, Thomas Arnesen
The X-linked lethal Ogden syndrome was the first reported human genetic disorder associated with a mutation in an N-terminal acetyltransferase (NAT) gene. The affected males harbor an Ser37Pro (S37P) mutation in the gene encoding Naa10, the catalytic subunit of NatA, the major human NAT involved in the co-translational acetylation of proteins. Structural models and molecular dynamics simulations of the human NatA and its S37P mutant highlight differences in regions involved in catalysis and at the interface between Naa10 and the auxiliary subunit hNaa15...
April 1, 2015: Human Molecular Genetics
https://www.readbyqxmd.com/read/25376646/naa10-controls-osteoblast-differentiation-and-bone-formation-as-a-feedback-regulator-of-runx2
#15
Haejin Yoon, Hye-Lim Kim, Yang-Sook Chun, Dong Hoon Shin, Kyoung-Hwa Lee, Chan Soo Shin, Dong Yeon Lee, Hong-Hee Kim, Zang Hee Lee, Hyun-Mo Ryoo, Mi-Ni Lee, Goo Taeg Oh, Jong-Wan Park
Runt-related transcription factor 2 (Runx2) transactivates many genes required for osteoblast differentiation. The role of N-α-acetyltransferase 10 (NAA10, arrest-defective-1), originally identified in yeast, remains poorly understood in mammals. Here we report a new NAA10 function in Runx2-mediated osteogenesis. Runx2 stabilizes NAA10 in osteoblasts during BMP-2-induced differentiation, and NAA10 in turn controls this differentiation by inhibiting Runx2. NAA10 delays bone healing in a rat calvarial defect model and bone development in neonatal mice...
2014: Nature Communications
https://www.readbyqxmd.com/read/25149475/meta-analysis-of-gwas-on-two-chinese-populations-followed-by-replication-identifies-novel-genetic-variants-on-the-x-chromosome-associated-with-systemic-lupus-erythematosus
#16
Yan Zhang, Jing Zhang, Jing Yang, Yongfei Wang, Lu Zhang, Xianbo Zuo, Liangdan Sun, Hai-Feng Pan, Nattiya Hirankarn, Tingyou Wang, Ruoyan Chen, Dingge Ying, Shuai Zeng, Jiangshan Jane Shen, Tsz Leung Lee, Chak Sing Lau, Tak Mao Chan, Alexander Moon Ho Leung, Chi Chiu Mok, Sik Nin Wong, Ka Wing Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Brian Hon-Yin Chung, Chun Yin Chong, Raymond Woon Sing Wong, Mo Yin Mok, Wilfred Hing Sang Wong, Kwok Lung Tong, Niko Kei Chiu Tse, Xiang-Pei Li, Yingyos Avihingsanon, Pornpimol Rianthavorn, Thavatchai Deekajorndej, Kanya Suphapeetiporn, Vorasuk Shotelersuk, Shirley King Yee Ying, Samuel Ka Shun Fung, Wai Ming Lai, Chun-Ming Wong, Irene Oi Lin Ng, Maria-Merce Garcia-Barcelo, Stacey S Cherny, Paul Kwong-Hang Tam, Pak Chung Sham, Sen Yang, Dong Qing Ye, Yong Cui, Xue-Jun Zhang, Yu Lung Lau, Wanling Yang
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22...
January 1, 2015: Human Molecular Genetics
https://www.readbyqxmd.com/read/25099252/de-novo-missense-mutations-in-the-naa10-gene-cause-severe-non-syndromic-developmental-delay-in-males-and-females
#17
Bernt Popp, Svein I Støve, Sabine Endele, Line M Myklebust, Juliane Hoyer, Heinrich Sticht, Silvia Azzarello-Burri, Anita Rauch, Thomas Arnesen, André Reis
Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes...
May 2015: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/24431331/a-splice-donor-mutation-in-naa10-results-in-the-dysregulation-of-the-retinoic-acid-signalling-pathway-and-causes-lenz-microphthalmia-syndrome
#18
Taraneh Esmailpour, Hamidreza Riazifar, Linan Liu, Sandra Donkervoort, Vincent H Huang, Shreshtha Madaan, Bassem M Shoucri, Anke Busch, Jie Wu, Alexander Towbin, Robert B Chadwick, Adolfo Sequeira, Marquis P Vawter, Guoli Sun, Jennifer J Johnston, Leslie G Biesecker, Riki Kawaguchi, Hui Sun, Virginia Kimonis, Taosheng Huang
INTRODUCTION: Lenz microphthalmia syndrome (LMS) is a genetically heterogeneous X-linked disorder characterised by microphthalmia/anophthalmia, skeletal abnormalities, genitourinary malformations, and anomalies of the digits, ears, and teeth. Intellectual disability and seizure disorders are seen in about 60% of affected males. To date, no gene has been identified for LMS in the microphthalmia syndrome 1 locus (MCOPS1). In this study, we aim to find the disease-causing gene for this condition...
March 2014: Journal of Medical Genetics
https://www.readbyqxmd.com/read/24408909/a-saccharomyces-cerevisiae-model-reveals-in-vivo-functional-impairment-of-the-ogden-syndrome-n-terminal-acetyltransferase-naa10-ser37pro-mutant
#19
Petra Van Damme, Svein I Støve, Nina Glomnes, Kris Gevaert, Thomas Arnesen
N-terminal acetylation (Nt-acetylation) occurs on the majority of eukaryotic proteins and is catalyzed by N-terminal acetyltransferases (NATs). Nt-acetylation is increasingly recognized as a vital modification with functional implications ranging from protein degradation to protein localization. Although early genetic studies in yeast demonstrated that NAT-deletion strains displayed a variety of phenotypes, only recently, the first human genetic disorder caused by a mutation in a NAT gene was reported; boys diagnosed with the X-linked Ogden syndrome harbor a p...
August 2014: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/23871722/xlid-causing-mutations-and-associated-genes-challenged-in-light-of-data-from-large-scale-human-exome-sequencing
#20
Amélie Piton, Claire Redin, Jean-Louis Mandel
Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past...
August 8, 2013: American Journal of Human Genetics
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