Read by QxMD icon Read


Daniela Boehm, Mark Jeng, Gregory Camus, Andrea Gramatica, Roland Schwarzer, Jeffrey R Johnson, Philip A Hull, Mauricio Montano, Naoki Sakane, Sara Pagans, Robert Godin, Steven G Deeks, Nevan J Krogan, Warner C Greene, Melanie Ott
Transcriptional latency of HIV is a last barrier to viral eradication. Chromatin-remodeling complexes and post-translational histone modifications likely play key roles in HIV-1 reactivation, but the underlying mechanisms are incompletely understood. We performed an RNAi-based screen of human lysine methyltransferases and identified the SET and MYND domain-containing protein 2 (SMYD2) as an enzyme that regulates HIV-1 latency. Knockdown of SMYD2 or its pharmacological inhibition reactivated latent HIV-1 in T cell lines and in primary CD4(+) T cells...
May 10, 2017: Cell Host & Microbe
Rui Wang, Xiaolan Deng, Yuichiro Yoshioka, Theodore Vougiouklakis, Jae-Hyun Park, Takehiro Suzuki, Naoshi Dohmae, Koji Ueda, Ryuji Hamamoto, Yusuke Nakamura
A specific subtype of non-small cell lung cancer (NSCLC) characterized with an EML4-ALK fusion gene, which drives constitutive oncogenic activation of ALK kinase, shows a good clinical response to ALK inhibitors. We have reported multiple examples implying the biological significance of methylation on non-histone proteins including oncogenic kinases in human carcinogenesis. Through the process to search substrates for various methyltransferases using an in vitro methyltransferase assay, we found that a lysine methyltransferase SMYD2 could methylate lysine residues 1451, 1455 and 1610 in ALK protein...
April 1, 2017: Cancer Science
Yuqiang Shan, Rongchao Ying, Zhong Jia, Wencheng Kong, Yi Wu, Sixin Zheng, Huicheng Jin
Gastric cancer (GC) is one of the most common malignant tumors of digestive system. The etiology of GC is complex and much more attention should be paid on the genetic factors. In this study, we explored the role and function of LINC00052 in GC. We applied qRT-PCR and northern blot to detect the expression of LINC00052 and found it was highly expressed during GC. We also investigated the effects of LINC00052 on tumor prognosis and progression, and found LINC00052 indicated poor prognosis and tumor progression...
March 23, 2017: Oncology Research
Adi Zipin-Roitman, Nasma Aqaqe, Muhammad Yassin, Shahar Biechonski, Mariam Amar, Mark F van Delft, Olga I Gan, Sean P McDermott, Alla Buzina, Troy Ketela, Liran Shlush, Stephanie Xie, Veronique Voisin, Jason Moffat, Mark D Minden, John E Dick, Michael Milyavsky
The molecular determinants governing escape of Acute Myeloid Leukemia (AML) cells from DNA damaging therapy remain poorly defined and account for therapy failures. To isolate genes responsible for leukemia cells regeneration following multiple challenges with irradiation we performed a genome-wide shRNA screen. Some of the isolated hits are known players in the DNA damage response (e.g. p53, CHK2), whereas other, e.g. SMYD2 lysine methyltransferase (KMT), remains uncharacterized in the AML context. Here we report that SMYD2 knockdown confers relative resistance to human AML cells against multiple classes of DNA damaging agents...
March 7, 2017: Oncotarget
Yi-Ching Lin, Yu-Chih Lin, Ming-Yii Huang, Po-Lin Kuo, Cheng-Chin Wu, Min-Sheng Lee, Chong-Chao Hsieh, Hsuan-Fu Kuo, Chang-Hung Kuo, Wen-Chan Tsai, Chih-Hsing Hung
The treatment of rheumatoid arthritis (RA) with tumor necrosis factor-alpha (TNF-α) inhibitors could lead to adverse effects. Therefore, the identification of downstream therapeutic targets is important. Monocyte chemoattractant protein-1 (MCP-1, also called CCL2) is related to RA disease activity, and epigenetic modifications are hypothesized to regulate gene expression in RA pathogenesis. We studied the effects of two TNF-α inhibitors, etanercept and adalimumab, on CCL2 expression and the potentially associated intracellular mechanisms, including epigenetic regulation...
March 2017: Molecular Immunology
Scott D Cowen, Daniel Russell, Leslie A Dakin, Huawei Chen, Nicholas A Larsen, Robert Godin, Scott Throner, Xiaolan Zheng, Audrey Molina, Jiaquan Wu, Tony Cheung, Tina Howard, Renee Garcia-Arenas, Nicholas Keen, Christopher S Pendleton, Jennifer A Pietenpol, Andrew D Ferguson
Protein lysine methyltransferases (KMTs) have emerged as important regulators of epigenetic signaling. These enzymes catalyze the transfer of donor methyl groups from the cofactor S-adenosylmethionine to specific acceptor lysine residues on histones, leading to changes in chromatin structure and transcriptional regulation. These enzymes also methylate an array of nonhistone proteins, suggesting additional mechanisms by which they influence cellular physiology. SMYD2 is reported to be an oncogenic methyltransferase that represses the functional activity of the tumor suppressor proteins p53 and RB...
December 22, 2016: Journal of Medicinal Chemistry
Balasubramanian Chandramouli, Giovanni Chillemi
Smyd2, the SET and MYND domain containing protein lysine methyltransferase, targets histone and nonhistone substrates. Methylation of nonhistone substrates has direct implications in cancer development and progression. Dynamic regulation of Smyd2 activity and the structural basis of broad substrate specificity still remain elusive. Herein, we report on extensive molecular dynamics simulations on a full length Smyd2 in the presence and absence of AdoMet cofactor (covering together 1.3 μs of sampling), and the accompanying conformational transitions...
December 27, 2016: Journal of Chemical Information and Modeling
Gregory T Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F Baas, Betti Giusti, Ewa Strauss, Femke N G Van't Hof, Thomas R Webb, Robert Erdman, Marylyn D Ritchie, James R Elmore, Anurag Verma, Sarah Pendergrass, Iftikhar J Kullo, Zi Ye, Peggy L Peissig, Omri Gottesman, Shefali S Verma, Jennifer Malinowski, Laura J Rasmussen-Torvik, Kenneth M Borthwick, Diane T Smelser, David R Crosslin, Mariza de Andrade, Evan J Ryer, Catherine A McCarty, Erwin P Böttinger, Jennifer A Pacheco, Dana C Crawford, David S Carrell, Glenn S Gerhard, David P Franklin, David J Carey, Victoria L Phillips, Michael J A Williams, Wenhua Wei, Ross Blair, Andrew A Hill, Thodor M Vasudevan, David R Lewis, Ian A Thomson, Jo Krysa, Geraldine B Hill, Justin Roake, Tony R Merriman, Grzegorz Oszkinis, Silvia Galora, Claudia Saracini, Rosanna Abbate, Raffaele Pulli, Carlo Pratesi, Athanasios Saratzis, Ana R Verissimo, Suzannah Bumpstead, Stephen A Badger, Rachel E Clough, Gillian Cockerill, Hany Hafez, D Julian A Scott, T Simon Futers, Simon P R Romaine, Katherine Bridge, Kathryn J Griffin, Marc A Bailey, Alberto Smith, Matthew M Thompson, Frank M van Bockxmeer, Stefan E Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D Blankensteijn, Joep A W Teijink, Cisca Wijmenga, Jacqueline de Graaf, Lambertus A Kiemeney, Jes S Lindholt, Anne Hughes, Declan T Bradley, Kathleen Stirrups, Jonathan Golledge, Paul E Norman, Janet T Powell, Steve E Humphries, Stephen E Hamby, Alison H Goodall, Christopher P Nelson, Natzi Sakalihasan, Audrey Courtois, Robert E Ferrell, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, John D Eicher, Andrew D Johnson, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Eric E Schadt, Johan L M Björkegren, Leonard Lipovich, Anne M Drolet, Eric L Verhoeven, Clark J Zeebregts, Robert H Geelkerken, Marc R van Sambeek, Steven M van Sterkenburg, Jean-Paul de Vries, Kari Stefansson, John R Thompson, Paul I W de Bakker, Panos Deloukas, Robert D Sayers, Seamus C Harrison, Andre M van Rij, Nilesh J Samani, Matthew J Bown
RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32...
January 20, 2017: Circulation Research
Tomoaki Fujii, Shin-Ichiro Tsunesumi, Hiroshi Sagara, Miyo Munakata, Yoshihiro Hisaki, Takao Sekiya, Yoichi Furukawa, Kazuhiro Sakamoto, Sumiko Watanabe
Methylation of histone tails plays a pivotal role in the regulation of a wide range of biological processes. SET and MYND domain-containing protein (SMYD) is a methyltransferase, five family members of which have been identified in humans. SMYD1, SMYD2, SMYD3, and SMYD4 have been found to play critical roles in carcinogenesis and/or the development of heart and skeletal muscle. However, the physiological functions of SMYD5 remain unknown. To investigate the function of Smyd5 in vivo, zebrafish were utilised as a model system...
2016: Scientific Reports
Kusal T G Samarasinghe, Dhanushka N P Munkanatta Godage, Yani Zhou, Fidelis T Ndombera, Eranthie Weerapana, Young-Hoon Ahn
Glucose metabolism and mitochondrial function are closely interconnected with cellular redox-homeostasis. Although glucose starvation, which mimics ischemic conditions or insufficient vascularization, is known to perturb redox-homeostasis, global and individual protein glutathionylation in response to glucose metabolism or mitochondrial activity remains largely unknown. In this report, we use our clickable glutathione approach, which forms clickable glutathione (azido-glutathione) by using a mutant of glutathione synthetase (GS M4), for detection and identification of protein glutathionylation in response to glucose starvation...
July 19, 2016: Molecular BioSystems
Hazem Ahmed, Shili Duan, Cheryl H Arrowsmith, Dalia Barsyte-Lovejoy, Matthieu Schapira
Protein methylation is a post-translational modification with important roles in transcriptional regulation and other biological processes, but the enzyme-substrate relationship between the 68 known human protein methyltransferases and the thousands of reported methylation sites is poorly understood. Here, we propose a bioinformatic approach that integrates structural, biochemical, cellular, and proteomic data to identify novel cellular substrates of the lysine methyltransferase SMYD2. Of the 14 novel putative SMYD2 substrates identified by our approach, six were confirmed in cells by immunoprecipitation: MAPT, CCAR2, EEF2, NCOA3, STUB1, and UTP14A...
June 3, 2016: Journal of Proteome Research
Erik Eggert, Roman C Hillig, Silke Koehr, Detlef Stöckigt, Jörg Weiske, Naomi Barak, Jeffrey Mowat, Thomas Brumby, Clara D Christ, Antonius Ter Laak, Tina Lang, Amaury E Fernandez-Montalvan, Volker Badock, Hilmar Weinmann, Ingo V Hartung, Dalia Barsyte-Lovejoy, Magdalena Szewczyk, Steven Kennedy, Fengling Li, Masoud Vedadi, Peter J Brown, Vijayaratnam Santhakumar, Cheryl H Arrowsmith, Timo Stellfeld, Carlo Stresemann
Protein lysine methyltransferases have recently emerged as a new target class for the development of inhibitors that modulate gene transcription or signaling pathways. SET and MYND domain containing protein 2 (SMYD2) is a catalytic SET domain containing methyltransferase reported to monomethylate lysine residues on histone and nonhistone proteins. Although several studies have uncovered an important role of SMYD2 in promoting cancer by protein methylation, the biology of SMYD2 is far from being fully understood...
May 26, 2016: Journal of Medicinal Chemistry
Ibrahim E Elsemman, Adil Mardinoglu, Saeed Shoaie, Taysir H Soliman, Jens Nielsen
Hepatitis C virus (HCV) infection is a worldwide healthcare problem; however, traditional treatment methods have failed to cure all patients, and HCV has developed resistance to new drugs. Systems biology-based analyses could play an important role in the holistic analysis of the impact of HCV on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular carcinoma (HCC)) and healthy liver tissue...
April 26, 2016: Molecular BioSystems
Nicolas Reynoird, Pawel K Mazur, Timo Stellfeld, Natasha M Flores, Shane M Lofgren, Scott M Carlson, Elisabeth Brambilla, Pierre Hainaut, Ewa B Kaznowska, Cheryl H Arrowsmith, Purvesh Khatri, Carlo Stresemann, Or Gozani, Julien Sage
Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with few therapeutic options. We found that levels of the lysine methyltransferase SMYD2 (SET and MYND domain 2) are elevated in PDAC and that genetic and pharmacological inhibition of SMYD2 restricts PDAC growth. We further identified the stress response kinase MAPKAPK3 (MK3) as a new physiologic substrate of SMYD2 in PDAC cells. Inhibition of MAPKAPK3 impedes PDAC growth, identifying a potential new kinase target in PDAC. Finally, we show that inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors...
April 1, 2016: Genes & Development
Wilson Oliveira-Santos, Doralina Amaral Rabello, Antônio Roberto Lucena-Araujo, Fábio Morato de Oliveira, Eduardo Magalhaes Rego, Fábio Pittella Silva, Felipe Saldanha-Araujo
SET and MYND domain containing 2 (SMYD2) and the SET and MYND domain containing 3 (SMYD3) are the most studied and well-characterized members of SMYD family. It has been demonstrated that their altered expression is associated with the progression of several solid tumors. Nevertheless, whether these methyltransferases exert any impact in chronic lymphocytic leukemia (CLL) remains unknown. Here, we investigated the gene expression profile of SMYD2 and SMYD3 in 59 samples of CLL and 10 normal B cells. The obtained results were associated with white blood cells (WBC) and platelet counts, ZAP-70 protein expression, and cytogenetic analysis...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Yuanyuan Jiang, Joshua Holcomb, Nicholas Spellmon, Zhe Yang
Methylation of estrogen receptor α by the histone lysine methyltransferase SMYD2 regulates ERα chromatin recruitment and its target gene expression. This protocol describes SMYD2 purification and crystallization of SMYD2 in complex with an ERα peptide. Recombinant SMYD2 is overexpressed in Escherichia coli cells. After release from the cells by French Press, SMYD2 is purified to apparent homogeneity with multiple chromatography methods. Nickel affinity column purifies SMYD2 based on specific interaction of its 6×His tag with the bead-immobilized nickel ions...
2016: Methods in Molecular Biology
Ana Sílvia Pires-Luís, Márcia Vieira-Coimbra, Filipa Quintela Vieira, Pedro Costa-Pinheiro, Rui Silva-Santos, Paula C Dias, Luís Antunes, Francisco Lobo, Jorge Oliveira, Céline S Gonçalves, Bruno M Costa, Rui Henrique, Carmen Jerónimo
Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC)...
2015: Epigenetics: Official Journal of the DNA Methylation Society
Eduardo Calpena, Francesc Palau, Carmen Espinós, Máximo Ibo Galindo
The Smyd gene family code for proteins containing a conserved core consisting of a SET domain interrupted by a MYND zinc finger. Smyd proteins are important in epigenetic control of development and carcinogenesis, through posttranslational modifications in histones and other proteins. Previous reports indicated that the Smyd family is quite variable in metazoans, so a rigorous phylogenetic reconstruction of this complex gene family is of central importance to understand its evolutionary history and functional diversification or conservation...
2015: PloS One
Sabine C Mueller, Christina Backes, Olga V Kalinina, Benjamin Meder, Daniel Stöckel, Hans-Peter Lenhof, Eckart Meese, Andreas Keller
BACKGROUND: High-throughput genetic testing is increasingly applied in clinics. Next-Generation Sequencing (NGS) data analysis however still remains a great challenge. The interpretation of pathogenicity of single variants or combinations of variants is crucial to provide accurate diagnostic information or guide therapies. METHODS: To facilitate the interpretation of variants and the selection of candidate non-synonymous polymorphisms (nsSNPs) for further clinical studies, we developed BALL-SNP...
2015: Genome Medicine
Ramzi F Sweis, Zhi Wang, Mikkel Algire, Cheryl H Arrowsmith, Peter J Brown, Gary G Chiang, Jun Guo, Clarissa G Jakob, Steven Kennedy, Fengling Li, David Maag, Bailin Shaw, Nirupama B Soni, Masoud Vedadi, William N Pappano
A lack of useful small molecule tools has precluded thorough interrogation of the biological function of SMYD2, a lysine methyltransferase with known tumor-suppressor substrates. Systematic exploration of the structure-activity relationships of a previously known benzoxazinone compound led to the synthesis of A-893, a potent and selective SMYD2 inhibitor (IC50: 2.8 nM). A cocrystal structure reveals the origin of enhanced potency, and effective suppression of p53K370 methylation is observed in a lung carcinoma (A549) cell line...
June 11, 2015: ACS Medicinal Chemistry Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"