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Wnt signaling and Loxl2 promote aggressive osteosarcoma

细胞研究（英文版） 2020年第10期30卷 885-901页

作者： Kazuhiko Matsuoka Latifa Bakiri Lena I.Wolff Markus Linder Amanda Mikels-Vigdal Ana Pati(n)o-García Fernando Lecanda Christine Hartmann Maria Sibilia Erwin F.Wagner Laboratory Genes and Disease Department of Dermatology Medical University of Vienna (MUV) Vienna 1090 Austria Genes Development and Disease Group Spanish National Cancer Research Centre (CNIO) Madrid 28029 Spain Laboratory Genes and Disease Department of Laboratory Medicine Medical University of Vienna (MUV) Vienna 1090 Austria Department of Bone and Skeletal Research Medical Faculty Institute of Musculoskeletal Medicine University of Münster Münster 48149 Germany Department of Medicine I Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna (MUV) Vienna 1090 Austria Gilead Sciences Inc. Foster City CA 94404 USA Navarra Institute for Health Research(IdISNA) and Program in Solid Tumors Center for Applied Medical Research (CIMA) University of Navarra Pamplona 31008 Spain Department of Pediatrics University Clinic of Navarra Pamplona 31008 Spain Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Pamplona 31008 Spain

Osteosarcoma (OS) is the most frequent primary malignant bone tumor in urgent need of better *** genetically modified mouse models (GEMMs),we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2.c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b andWnt9a in OS cells through promoter binding,and Wnt7b and Wnt9a in tum promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and ***,inhibition of Wnt ligand secretion by inactivating the Wnt-less (Wls) gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of ***-deficient osteosarcomas proliferate less,are less mineralized and are enriched in fibroblastic cells surrounded by collagen ***,Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation ***,OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking ***,a strong correlation between c-FOS,LOXL2 and WNT7B/WNT9A expression is observed in human OS samples,and c-FOS/LOXL2 coexpression correlates with OS aggressiveness and decreased patient ***,therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric,recurrent,and metastatic OS.

关键词： Bone cancer Mechanisms of disease

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Comprehensive behavioral analysis of heterozygous Syngap1 knockout mice

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Neuropsychopharmacology Reports 2019年第3期39卷 223-237页

作者： Nakajima, Ryuichi Takao, Keizo Hattori, Satoko Shoji, Hirotaka Komiyama, Noboru H. Grant, Seth G. N. Miyakawa, Tsuyoshi Division of Systems Medical Science Institute for Comprehensive Medical Science Fujita Health University Toyoake Japan Division of Animal Resources and Development Life Science Research Center University of Toyama Toyama Japan Section of Behavior Patterns Center for Genetic Analysis of Behavior National Institute for Physiological Sciences Okazaki Japan Centre for Clinical Brain Sciences The Patrick Wild Centre for Research into Autism Fragile X Syndrome & Intellectual Disabilities The University of Edinburgh Edinburgh United Kingdom Genes to Cognition Program Centre for Clinical Brain Sciences University of Edinburgh Edinburgh United Kingdom

Aims: Synaptic Ras GTPase-activating protein 1 (SYNGAP1) regulates synaptic plasticity through AMPA receptor trafficking. SYNGAP1 mutations have been found in human patients with intellectual disability (ID) and autism spectrum disorder (ASD). Almost every individual with SYNGAP1-related ID develops epilepsy, and approximately 50% have ASD. SYNGAP1-related ID is estimated to account for at least 1% of ID cases. In mouse models with Syngap1 mutations, strong cognitive and affective dysfunctions have been reported, yet some findings are inconsistent across studies. To further understand the behavioral significance of the SYNGAP1 gene, we assessed various domains of behavior in Syngap1 heterozygous mutant mice using a behavioral test battery. Methods: Male mice with a heterozygous mutation in the Syngap1 gene (Syngap1^−/+ mice) created by Seth Grant's group were subjected to a battery of comprehensive behavioral tests, which examined general health, and neurological screens, rotarod, hot plate, open field, light/dark transition, elevated plus maze, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, gait analysis, T-maze, Y-maze, Barnes maze, contextual and cued fear conditioning, and home cage locomotor activity. To control for type I errors due to multiple-hypothesis testing, P-values below the false discovery rate calculated by the Benjamini-Hochberg method were considered as study-wide statistically significant. Results: Syngap1^−/+ mice showed increased locomotor activity, decreased prepulse inhibition, and impaired working and reference spatial memory, consistent with preceding studies. Impairment of context fear memory and increased startle reflex in Syngap1 mutant mice could not be reproduced. Significant decreases in sensitivity to painful stimuli and impaired motor function were observed in Syngap1^−/+ mice. Decreased anxiety-like behavior and depression-like behavior were noted, although increased loco

关键词： autism spectrum disorder intellectual disability motor function nociception SYNGAP1

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An integrated transcriptomic cell atlas of human neural organoids (vol 635, pg 690, 2024)

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NATURE 2025年第8045期637卷 E21-E21页

作者： He, Zhisong Dony, Leander Fleck, Jonas Simon Szalata, Artur Li, Katelyn X. Sliskovic, Irena Lin, Hsiu-Chuan Santel, Malgorzata Atamian, Alexander Quadrato, Giorgia Sun, Jieran Pasca, Sergiu P. Camp, J. Gray Theis, Fabian J. Treutlein, Barbara Department of Biosystems Science and Engineering ETH Zürich Basel Switzerland Institute of Computational Biology Computational Health Center Helmholtz Munich Neuherberg Germany Department Genes and Environment Max Planck Institute of Psychiatry Munich Germany International Max Planck Research School for Translational Psychiatry (IMPRS-TP) Munich Germany TUM School of Life Sciences Weihenstephan Technical University of Munich Freising Germany School of Computation Information and Technology Technical University of Munich Munich Germany Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden Institute of Human Biology (IHB) Roche Pharma Research and Early Development Roche Innovation Center Basel Basel Switzerland Biozentrum University of Basel Basel Switzerland Department of Stem Cell Biology and Regenerative Medicine Keck School of Medicine University of Southern California Los Angeles CA USA Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC Keck School of Medicine University of Southern California Los Angeles CA USA Department of Psychiatry and Behavioral Sciences Stanford University Stanford CA USA Stanford Brain Organogenesis Program Wu Tsai Neurosciences Institute and Bio-X Stanford CA USA Neural Stem Cell Institute Albany NY USA UK Dementia Research Institute at the University of Edinburgh Edinburgh Bioquarter Edinburgh UK Centre for Discovery Brain Sciences School of Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Edinburgh UK Human Technopole Milan Italy Department of Oncology and Hemato-Oncology University of Milan Milan Italy

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Correction to: Mapping of dressed and processed poultry products in Bangladesh: Identifying the food safety risks for policy intervention

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Veterinary research communications 2023年第4期47卷 2003页

作者： Jinnat Ferdous Helal Uddin Rashed Mahmud Mathew Hennessey Abdullah Al Sattar Suman Das Gupta Justine S Gibson Robyn Alders Joerg Henning Guillaume Fournié Ahasanul Hoque School of Veterinary Science The University of Queensland Queensland Australia. j.ferdous@uq.edu.au. Chattogram Veterinary and Animal Sciences University Chittagong Bangladesh. Veterinary Epidemiology Economics and Public Health Group Department of Pathobiology and Population Sciences Royal Veterinary College London UK. School of Veterinary Science The University of Queensland Queensland Australia. Gulbali Institute Charles Sturt University Wagga Wagga NSW Australia. Development Policy Centre Australian National University Canberra NSW Australia. Global Health Program Chatham House London UK. INRAE VetAgro Sup UMR EPIA Université de Lyon Marcy l'Etoile 69280 France. INRAE VetAgro Sup UMR EPIA Université Clermont Auvergne Saint Genes Champanelle 63122 France.

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Linking seed size and number to trait syndromes in trees

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Global Ecology and Biogeography 2023年第5期32卷

作者： Michal Bogdziewicz Marie-Claire Aravena Acuña Robert Andrus Davide Ascoli Yves Bergeron Daniel Brveiller Thomas Boivin Raul Bonal Thomas Caignard Maxime Cailleret Rafael Calama Sergio Donoso Calderon J. Julio Camarero Chia-Hao Chang-Yang Jerome Chave Francesco Chianucci Natalie L. Cleavitt Benoit Courbaud Andrea Cutini Thomas Curt Adrian J. Das Hendrik Davi Nicolas Delpierre Sylvain Delzon Michael Dietze Laurent Dormont William Farfan-Rios Catherine A. Gehring Gregory S. Gilbert Georg Gratzer Cathryn H. Greenberg Arthur Guignabert Qinfeng Guo Andrew Hacket-Pain Arndt Hampe Qingmin Han Kazuhiko Hoshizaki Ines Ibanez Jill F. Johnstone Valentin Journé Thomas Kitzberger Johannes M. H. Knops Georges Kunstler Richard Kobe Jonathan G. A. Lageard Jalene M. LaMontagne Mateusz Ledwon Theodor Leininger Jean-Marc Limousin James A. Lutz Diana Macias Anders Marell Eliot J. B. McIntire Emily Moran Renzo Motta Jonathan A. Myers Thomas A. Nagel Shoji Naoe Mahoko Noguchi Michio Oguro Hiroko Kurokawa Jean-Marc Ourcival Robert Parmenter Ignacio M. Perez-Ramos Lukasz Piechnik Tomasz Podgórski John Poulsen Tong Qiu Miranda D. Redmond Chantal D. Reid Kyle C. Rodman Pavel Šamonil Jan Holik C. Lane Scher Harald Schmidt Van Marle Barbara Seget Mitsue Shibata Shubhi Sharma Miles Silman Michael A. Steele Jacob N. Straub I-Fang Sun Samantha Sutton Jennifer J. Swenson Peter A. Thomas Maria Uriarte Giorgio Vacchiano Thomas T. Veblen Boyd Wright S. Joseph Wright Thomas G. Whitham Kai Zhu Jess K. Zimmerman Magdalna Zywiec James S. Clark Institut National de Recherche pour Agriculture Alimentation et Environnement (INRAE) Laboratoire EcoSystemes et Societes En Montagne (LESSEM) Universite Grenoble Alpes Grenoble France Forest Biology Center Faculty of Biology Adam Mickiewicz University Poznan Poland Laboratorio de Recursos Agroforestales Centro Austral de Investigaciones Científicas (CADIC – CONICET) Ushuaia Argentina INRAE UR EFNO Nogent-sur-Vernisson France Department of Agriculture Forest and Food Sciences University of Torino Grugliasco Italy Université du Québec en Abitibi-Témiscamingue Rouyn-Noranda Québec Canada Université du Québec à Montréal Montreal Québec Canada CNRS Université Paris-Saclay AgroParisTech Paris France INRAE UR 629 Ecologie des Forêts Méditerranéennes Avignon France Department of Biodiversity Ecology and Evolution Faculty of Biological Sciences Complutense University of Madrid Madrid Spain Institut National de Recherche pour Agriculture Alimentation et Environnement (INRAE) Biodiversity Genes and Communities (BIOGECO) Universite Bordeaux Pessac France INRAE Aix-Marseille University UMRRECOVER Aix-en-Provence France Instituto de Ciencias Forestales. INIA-CSIC Madrid Spain Facultad de Ciencias Forestales y de la Conservacion de la Naturaleza (FCFCN) Universidad de Chile Santiago Chile Consejo Superior de Investigaciones Científicas (IPE-CSIC) Instituto Pirenaico de Ecología Zaragoza Spain Department of Biological Sciences National Sun Yat-sen University Kaohsiung Taiwan Laboratoire Évolution et Diversité Biologique UMR 5174 (CNRS/IRD/UPS) CNRS Toulouse France CREA Research centre for Forestry and Wood Arezzo Italy DNRE Cornell University Ithaca New York USA Institut National de Recherche pour Agriculture Alimentation et Environnement (INRAE) Aix Marseille Universite Aix-en-Provence France U.S. Geological Survey Western Ecological Research Center California Three Rivers USA INRAE Ecologie des Forets Mediterranennes Avignon France CNRS AgroPari

Aim Our understanding of the mechanisms that maintain forest diversity under changing climate can benefit from knowledge about traits that are closely linked to fitness. We tested whether the link between traits and seed number and seed size is consistent with two hypotheses, termed the leaf economics spectrum and the plant size syndrome, or whether reproduction represents an independent dimension related to a seed size–seed number trade-off. Location Most of the data come from Europe, North and Central America and East Asia. A minority of the data come from South America, Africa and Australia. Time period 1960–2022. Major taxa studied Trees. Methods We gathered 12 million observations of the number of seeds produced in 784 tree species. We estimated the number of seeds produced by individual trees and scaled it up to the species level. Next, we used principal components analysis and generalized joint attribute modelling (GJAM) to map seed number and size on the tree traits spectrum. Results Incorporating seed size and number into trait analysis while controlling for environment and phylogeny with GJAM exposes relationships in trees that might otherwise remain hidden. Production of the large total biomass of seeds [product of seed number and seed size; hereafter, species seed productivity (SSP)] is associated with high leaf area, low foliar nitrogen, low specific leaf area (SLA) and dense wood. Production of high seed numbers is associated with small seeds produced by nutrient-demanding species with softwood, small leaves and high SLA. Trait covariation is consistent with opposing strategies: one fast-growing, early successional, with high dispersal, and the other slow-growing, stress-tolerant, that recruit in shaded conditions. Main conclusions Earth system models currently assume that reproductive allocation is indifferent among plant functional types. Easily measurable seed size is a strong predictor of the seed number and species seed productivity. The connectio

关键词： fecundity functional traits leaf economics life history strategies size syndrome tree recruitment

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Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women

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Genomics 2020年第2期112卷 1223-1232页

作者： Jason Y Y Wong Han Zhang Chao A Hsiung Kouya Shiraishi Kai Yu Keitaro Matsuo Maria Pik Wong Yun-Chul Hong Jiucun Wang Wei Jie Seow Zhaoming Wang Minsun Song Hee Nam Kim I-Shou Chang Nilanjan Chatterjee Wei Hu Chen Wu Tetsuya Mitsudomi Wei Zheng Jin Hee Kim Adeline Seow Neil E Caporaso Min-Ho Shin Lap Ping Chung She-Juan An Ping Wang Yang Yang Hong Zheng Yasushi Yatabe Xu-Chao Zhang Young Tae Kim Qiuyin Cai Zhihua Yin Young-Chul Kim Bryan A Bassig Jiang Chang James Chung Man Ho Bu-Tian Ji Yataro Daigo Hidemi Ito Yukihide Momozawa Kyota Ashikawa Yoichiro Kamatani Takayuki Honda H Dean Hosgood Hiromi Sakamoto Hideo Kunitoh Koji Tsuta Shun-Ichi Watanabe Michiaki Kubo Yohei Miyagi Haruhiko Nakayama Shingo Matsumoto Masahiro Tsuboi Koichi Goto Jianxin Shi Lei Song Xing Hua Atsushi Takahashi Akiteru Goto Yoshihiro Minamiya Kimihiro Shimizu Kazumi Tanaka Fusheng Wei Fumihiko Matsuda Jian Su Yeul Hong Kim In-Jae Oh Fengju Song Wu-Chou Su Yu-Min Chen Gee-Chen Chang Kuan-Yu Chen Ming-Shyan Huang Li-Hsin Chien Yong-Bing Xiang Jae Yong Park Sun-Seog Kweon Chien-Jen Chen Kyoung-Mu Lee Batel Blechter Haixin Li Yu-Tang Gao Biyun Qian Daru Lu Jianjun Liu Hyo-Sung Jeon Chin-Fu Hsiao Jae Sook Sung Ying-Huang Tsai Yoo Jin Jung Huan Guo Zhibin Hu Wen-Chang Wang Charles C Chung Laurie Burdett Meredith Yeager Amy Hutchinson Sonja I Berndt Wei Wu Herbert Pang Yuqing Li Jin Eun Choi Kyong Hwa Park Sook Whan Sung Li Liu C H Kang Meng Zhu Chung-Hsing Chen Tsung-Ying Yang Jun Xu Peng Guan Wen Tan Chih-Liang Wang Michael Hsin Ko-Yung Sit James Ho Ying Chen Yi Young Choi Jen-Yu Hung Jun Suk Kim Ho Il Yoon Chien-Chung Lin In Kyu Park Ping Xu Yuzhuo Wang Qincheng He Reury-Perng Perng Chih-Yi Chen Roel Vermeulen Junjie Wu Wei-Yen Lim Kun-Chieh Chen Yao-Jen Li Jihua Li Hongyan Chen Chong-Jen Yu Li Jin Tzu-Yu Chen Shih-Sheng Jiang Jie Liu Taiki Yamaji Belynda Hicks Kathleen Wyatt Shengchao A Li Juncheng Dai Hongxia Ma Guangfu Jin Bao Song Zhehai Wang Sensen Cheng Xuelian Li Yangwu Ren Ping Cui Motoki Iwasaki Taichi Shimazu Shoichiro Tsugane Junjie Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA. Electronic address: jason.wong@nih.gov. Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA. Institute of Population Health Sciences National Health Research Institutes Zhunan Taiwan. Division of Genome Biology National Cancer Center Research Institute Tokyo Japan. Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan Department of Cancer Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan. Department of Pathology Queen Mary Hospital The University of Hong Kong Hong Kong. Department of Preventive Medicine Seoul National University College of Medicine Seoul Republic of Korea. Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai China State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai China. Saw Swee Hock School of Public Health National University of Singapore Singapore. Cancer Genomics Research Laboratory Leidos Biomedical Research Inc Gaithersburg MD USA Department of Computational Biology St. Jude Children's Research Hospital Memphis TN USA. Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA Department of Statistics Sookmyung Women's University Seoul Republic of Korea. Department of Preventive Medicine Chonnam National University Medical School Gwangju Republic of Korea. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Bloomberg School of Public Health Johns Hopkins University Baltimore MD USA. Department of Etiology & Carcinogenesis and State Key Laboratory of Molecular Oncology Cancer Institute and Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China. Division of Thoracic Surgery Kinki University School of Medicine Sayama Japan. Division of

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

关键词： Lung adenocarcinoma Lung cancer Mendelian randomization Pathway analysis Tuberculosis

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ISDN2014_0312: Phasic dopamine neuron activity elicits unique mesofrontal plasticity in adolescence

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International Journal of developmental Neuroscience 2015年第PART_A期47卷

作者： Surjeet Mastwal Yizhou Ye Ming Ren Dennisse Jimenez Keri Martinowich Charles R. Gerfen Kuan Hong Wang Unit on Neural Circuits and Adaptive Behaviors Genes Cognition and Psychosis Program National Institute of Mental Health National Institutes of Health Bethesda MD 20892 USA Lieber Institute for Brain Development The Johns Hopkins University School of Medicine Baltimore MD 21205 USA Departments of Psychiatry & Behavioral Sciences and Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA Laboratory of Systems Neuroscience National Institute of Mental Health National Institutes of Health Bethesda MD 20892 USA

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Role of a BRCA1 associated deubiquitinating complex in DNA damage response

Role of a BRCA1 associated deubiquitinating complex in DNA d...

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2013年全球华人生物科学家大会

作者： Castillo A Hu X Paul A Wu L Sun B Wang B Department of Genetics The University of Texas M.D.Anderson Cancer Center Department of GeneticsThe University of Texas M.D.Anderson Cancer Center Genes and Development Program The University of Texas Graduate School of Biomedical SciencesHoustonTexas 77030USA

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A4.9 How Osteoblast Regulates Energy Metabolism and Systemic Inflammation Dependent of FRA-2 Expression

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Annals of the Rheumatic Diseases 2013年 72卷 A27-A27页

作者： Aline Bozec Yubin Luo Christine Zech Maria Jimenez Latifa Bakiri Mirco Petrucelli Michael Amling Georg Schett Erwin Wagner 1Department of Medicine 3 Rheumatology and Immunology University of Erlangen-Nuremberg Nikolaus-Fiebiger-ZentrumGlueckstrasse 6 D-91054 Erlangen Germany 2Genes Development and Disease Group F-BBVA-CNIO Cancer Cell Biology Program Spanish National Cancer Research Centre (CNIO) E-28029 Madrid 3Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Martinistrasse 52 D-20246 Hamburg Germany

Background and Objectives The transcription factor Fra-2 (Fosl2) is a member of the AP-1 complex and an important regulator of bone homeostasis. We have previously shown that Fra-2 controls bone development, osteoclast size [1] and osteoblast differentiation through direct regulation of Collagen 1a2 and Osteocalcin (Ocn) [2]. Recent studies have established that the skeleton functions as an endocrine organ affecting metabolism through Ocn [3], although only few transcription factors and only one osteoblast-derived hormone are known to affect the crosstalk between bone and metabolism. Materials and Methods We have generated mice with specific deletion of Fra-2 ( Fosl2 ) or ectopic expression of Fra-2 in osteoblast to study the role of Fra-2 beyond the bone e.g. in metabolism. Results Here we show that mice with osteoblast specific deletion of Fra-2 ( Fosl2 ) have despite a low bone mass, an increased body weight. In contrast, ectopic expression of Fra-2 in osteoblasts display increased bone mass and decreased body weight accompanied with reduced serum glucose and insulin levels, improved glucose tolerance and insulin sensitivity. In addition, these Fra-2 mutant mice are protected from metabolic impairment, when challenged with high fat diet (HFD). Surprisingly a systemic inflammation and macrophage infiltration in liver, spleen and lung was observed in Fra-2 osteoblast specific mice. Mechanistically, we showed that in osteoblasts Fra-2 transcriptionally represses an important adipo-cytokine Adiponectin (Adipoq), while it induces Ocn, both responsible for the glucose and insulin metabolism alteration. Whereas, the systemic inflammation was likely due to the transcriptional increased of Osteopontin (OPN) expression by Fra-2, which is known as a potent inductor of macrophage activation. Conclusions Taking together these results show that Fra-2 expression in osteoblast transcriptionally modulates Adipoq, Ocn and OPN expression and secretion representing a novel mechanism

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Lysine methylation: beyond histones

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生物化学与生物物理学报（英文版） 2012年第1期44卷 14-27页

作者： Xi Zhang Hong Wen Xiaobing Shi Department of Biochemistry & Molecular Biology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Centers for Cancer Epigenetics and Stem Cell and Developmental Biology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Department of Biochemistry & Molecular Biology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Centers for Cancer Epigenetics and Stem Cell and Developmental Biology University of Texas MD Anderson Cancer Center Houston TX 77030 USA Program in Genes and Development Graduate School of Biomedical Sciences University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Posttranslational modifications (PTMs) of histone proteins, such as acetylation, methylation, phosphorylation, and ubiquitylation, play essential roles in regulating chromatin dynamics. Combinations of different modifications on the histone proteins, termed ‘histone code’ in many cases, extend the information potential of the genetic code by regulating DNA at the epigenetic level. Many PTMs occur on non-histone proteins as well as histones, regulating protein–protein interactions, stability, localization, and/or enzymatic activities of proteins involved in diverse cellular processes. Although protein phosphorylation, ubiquitylation, and acetylation have been extensively studied, only a few proteins other than histones have been reported that can be modified by lysine methylation. This review summarizes the current progress on lysine methylation of non-histone proteins, and we propose that lysine methylation, like phosphorylation and acetylation, is a common PTM that regulates proteins in diverse cellular processes.

关键词： methylation lysine methyltransferase (KMT) lysine demethylase (KDM) p53 epigenetics

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