Article
Cell Biology
Lei Wu, Fan Kou, Zhenyu Ji, Baihui Li, Bailu Zhang, Yan Guo, Lili Yang
Summary: The study showed that SMYD2 is significantly upregulated in lung adenocarcinoma (LUAD), and its high expression is associated with shorter survival rates in patients. RNA-seq and chromatin immunoprecipitation-quantitative PCR revealed that SMYD2 may promote tumor cell proliferation and metastasis by activating RPS7.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Medicinal
Quan Zheng, Wen Zhang, Guo-Wu Rao
Summary: This article reviews the current research status of protein methyltransferase SMYD2 and the development of inhibitors. It evaluates the challenges in this field and provides insights into future directions.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ming Tang, Guofang Chen, Bo Tu, Zhiyi Hu, Yujia Huang, Christopher C. DuFort, Xiaoping Wan, Zhiyong Mao, Yongzhong Liu, Wei-Guo Zhu, Wen Lu
Summary: DDR has different effects on cancer susceptibility and drug resistance. Recent studies showed that DDR inhibitors impact immune surveillance, however, the underlying mechanism is poorly understood. This study reveals that methyltransferase SMYD2 plays a crucial role in nonhomologous end joining repair (NHEJ), promoting tumor cell adaptability to radiotherapy. SMYD2 is mobilized to chromatin upon DNA damage and methylates Ku70, leading to increased recruitment of Ku70/Ku80/DNA-PKcs complex. Inhibition of SMYD2 or knockdown of SMYD2 results in persistent DNA damage and improper repair, leading to cytosolic DNA accumulation and activation of cGAS-STING pathway, triggering antitumor immunity by infiltration and activation of cytotoxic CD8+ T cells. This study reveals a novel role of SMYD2 in regulating NHEJ pathway and innate immune responses, suggesting SMYD2 as a promising therapeutic target for cancer treatment.
Article
Cell Biology
Yong Ji, Xiaofeng Xu, Cong Long, Jianjiang Wang, Li Ding, Zhizhong Zheng, Huiping Wu, Liu Yang, Lan Tao, Feng Gao
Summary: This study analyzed the effect of SMYD2 on gastrointestinal stromal tumors (GIST) and found that it can accelerate GIST by regulating the expression of EZH2 and TET1. This finding provides new treatment opportunities for GIST.
CELL DEATH DISCOVERY
(2022)
Article
Cell Biology
Haibi Su, Chen Meng, Jie Xu, Zhenghua Su, Chenxi Xiao, Di Yang
Summary: The study reveals that Smyd2 plays an important regulatory role in adipogenesis and adipocyte differentiation. Inhibition of Smyd2 can hinder adipocyte differentiation, thereby slowing down the occurrence and development of obesity.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Marloes van den Berg, Eva L. Peters, Robbert J. van der Pijl, Shengyi Shen, Leo M. A. Heunks, Henk L. Granzier, Coen A. C. Ottenheijm
Summary: Diaphragm weakness frequently occurs in mechanically ventilated critically ill patients, and this study suggests that modulating titin stiffness may affect its development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Vincent Loreau, Renate Rees, Eunice HoYee Chan, Waltraud Taxer, Kathrin Gregor, Bianka Mussil, Christophe Pitaval, Nuno Miguel Luis, Pierre Mangeol, Frank Schnorrer, Dirk Goerlich
Summary: Measuring the positions and dynamics of proteins in intact tissues or whole animals is challenging due to limited accessibility of large antibodies and potential interference of fluorescent proteins. In this study, a toolbox of nanobodies targeting different domains of key sarcomeric proteins was introduced, showing superior labeling qualities compared to antibodies. The toolbox was used to study sarcomere morphogenesis and revealed the presence of a gigantic isoform of Sallimus and the polar orientation of Projectin. The nanobodies were also shown to have high affinity-binding without affecting protein function.
Article
Cardiac & Cardiovascular Systems
Brandon Y. H. Chan, Andrej Roczkowsky, Woo Jung Cho, Mathieu Poirier, Consolato Sergi, Vic Keschrumrus, Jared M. Churko, Henk Granzier, Richard Schulz
Summary: The study found that MMP inhibitors can protect against DXR cardiotoxicity by reducing cardiac dysfunction and left ventricular remodelling, preventing myocardial fibrosis. This suggests that MMP inhibitors may be a potential prophylactic strategy to prevent heart injury during chemotherapy.
CARDIOVASCULAR RESEARCH
(2021)
Article
Plant Sciences
Weiwei Xu, Rui Peng, Siyu Chen, Congcong Wu, Xiaoxiao Wang, Ting Yu, Jiuying Jian, Ni Zhang, Siyang Zuo, Min Chen, Bing Guo, Lirong Liu
Summary: This study found that RTT extract has antifibrotic and anti-inflammatory effects on diabetic nephropathy, possibly through suppressing SMYD2 activation and H3K36me3 and H3K4me3 protein expression.
PHARMACEUTICAL BIOLOGY
(2022)
Article
Biology
Florian Schueder, Pierre Mangeol, Eunice HoYee Chan, Renate Rees, Juergen Schuenemann, Ralf Jungmann, Dirk Goerlich, Frank Schnorrer
Summary: Sarcomeres, the force-producing units of striated muscles, depend on the titin protein for their nanoarchitecture. This study used nanobodies and super-resolution microscopy to determine the location of two Drosophila titin homologs in flight muscles. The findings reveal the presence of these titin homologs and their role in muscle structure, providing insights into the organization of sarcomeres in non-vertebrates.
Article
Biochemical Research Methods
Feng Gao, Mengyang Chang, Xiang Meng, Hang Xu, Giri Gnawali, Yue Dong, Byrdie Lopez, Wei Wang
Summary: This article reports a method for selectively modifying secondary amines in peptides, proteins, and natural products. By fine-tuning the electronic effect of ynones, the reactivity of the Michael acceptor can be controlled for selective reaction with structurally different secondary amines in complex structures and biological environments.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Cell Biology
Jiacheng Wu, Ye Hu, Jiaying Song, Jia Xu, Qian Zhang, Yangyang Chai, Xin Wang, Bingjing Wang, Yong Zhao, Xuetao Cao, Xiaoqing Xu
Summary: Phosphorylation of IRF3 is critical for inducing IFN-I production in antiviral innate response. This study identifies SMYD2 as a negative regulator of IFN-I production by inhibiting IRF3 phosphorylation in macrophages during viral infections. SMYD2 interacts with IRF3 domains and recruits phosphatase PP1α to decrease IRF3 phosphorylation, thereby modulating the antiviral innate response.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Kwangho Kim, Tae Young Ryu, Eunsun Jung, Tae-Su Han, Jinkwon Lee, Seon-Kyu Kim, Yu Na Roh, Moo-Seung Lee, Cho-Rok Jung, Jung Hwa Lim, Ryuji Hamamoto, Hye Won Lee, Keun Hur, Mi-Young Son, Dae-Soo Kim, Hyun-Soo Cho
Summary: A protein called SMYD2 has been identified as a potential target for novel therapies for non-small-cell lung cancer (NSCLC) due to its role in promoting cancer spread. In laboratory experiments, inhibiting SMYD2 production in lung cancer cells hindered the process of metastasis. This discovery could lead to new treatment options for this form of lung cancer.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Biophysics
Atsuki Fukutani, Walter Herzog
Summary: The study aimed to examine the magnitude of the stretch-shortening cycle (SSC) effect in inhibited skeletal muscle force states. Results indicated that the SSC effect was preserved in the reduced force state and was significantly greater compared to the normal force state.
JOURNAL OF BIOMECHANICS
(2021)
Article
Developmental Biology
Nuno Miguel Luis, Frank Schnorrer
Summary: Muscles generate forces through sarcomeres to drive animal locomotion. During muscle development, sarcomeres assemble into long periodic myofibrils that mechanically connect to skeleton elements. Tension coordinates assembly of key sarcomeric components and transcriptional feedback mechanisms help coordinate myofibril assembly and maturation.
CELLS & DEVELOPMENT
(2021)
Review
Cardiac & Cardiovascular Systems
Christine M. Loescher, Anastasia J. Hobbach, Wolfgang A. Linke
Summary: This review provides an overview of the changes in cardiac titin properties at a molecular level, including the role isoform diversity and post-translational modifications play in regulating myocardial function, and discusses the importance of this regulation imbalance in heart disease.
CARDIOVASCULAR RESEARCH
(2022)
Review
Physiology
Sebastian Koetter, Martina Krueger
Summary: This review explores the composition of the sarcomere, the smallest molecular unit of muscle contraction and relaxation, and focuses on the role of the sarcomere protein titin and its relationship with protein quality control. It summarizes the current state of research on titin turnover and discusses the involvement of various intracellular degradation mechanisms. Additionally, it examines how perturbations in protein quality control can affect sarcomeric proteins, particularly titin, in different disease states.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Florian Funk, Annette Kronenbitter, Malgorzata Isic, Vera Flocke, Simone Gorressen, Dominik Semmler, Maximilian Brinkmann, Katharina Beck, Oliver Steinhoff, Tanu Srivastava, David Monteiro Barbosa, Katharina Voigt, Luzhou Wang, Katharina Bottermann, Sebastian Koetter, Maria Grandoch, Ulrich Floegel, Martina Krueger, Joachim P. Schmitt
Summary: Type 2 diabetes mellitus is associated with adverse clinical outcome after myocardial infarction. This study found that in diabetic mice, the calcium cycling of cardiomyocytes was impaired, but contractile function was preserved due to increased myofilament calcium sensitivity and higher responsiveness to beta-adrenergic stimulation. However, ischemia-reperfusion further impaired cardiomyocyte function and calcium handling in diabetic mice, as these compensatory mechanisms failed.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Multidisciplinary Sciences
Anthony L. Hessel, Weikang Ma, Nicole Mazara, Paige E. Rice, Devin Nissen, Henry Gong, Michel Kuehn, Thomas Irving, Wolfgang A. Linke
Summary: This study found that skeletal muscle force production increases with longer muscle lengths due to length-dependent priming of thick filament proteins in the muscle unit before contraction. The research also discovered that bridge proteins between thick and thin filaments, potentially myosin-binding protein C, play a role in the length-dependent priming of thin filaments. These bridges can be forcibly ruptured via high-speed stretches.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Matthias Rohrbeck, Verena Hoerr, Ilaria Piccini, Boris Greber, Jan Sebastian Schulte, Sara-Sophie Huebner, Elena Jeworutzki, Carsten Theiss, Veronika Matschke, Joerg Stypmann, Andreas Unger, Huyen Tran Ho, Paul Disse, Nathalie Strutz-Seebohm, Cornelius Faber, Frank Ulrich Mueller, Stephan Ludwig, Ursula Rescher, Wolfgang A. A. Linke, Karin Klingel, Karin Busch, Stefan Peischard, Guiscard Seebohm
Summary: Using a transgenic mouse strain (TG) containing a CVB3 Delta VP0 genome, we have revealed virus-mediated cardiac pathophysiological processes in vivo and in vitro. Transgenic mice showed significant alterations in cardiac function, pathologic ECG alterations, calcium homeostasis, intracellular organization, and gene expression. The results also suggest that mitochondrial impairment may contribute to cardiac contractile dysfunction.
Review
Cardiac & Cardiovascular Systems
Sabine Steffens, Katrin Schroeder, Martina Krueger, Christoph Maack, Katrin Streckfuss-Boemeke, Johannes Backs, Rolf Backofen, Bettina Baessler, Yvan Devaux, Ralf Gilsbach, Jordi Heijman, Jochen Knaus, Rafael Kramann, Dominik Linz, Allyson L. Lister, Henrike Maatz, Lars Maegdefessel, Manuel Mayr, Benjamin Meder, Sara Y. Nussbeck, Eva A. Rog-Zielinska, Marcel H. Schulz, Albert Sickmann, Goekhan Yigit, Peter Kohl
Summary: Sharing and documentation of cardiovascular research data are essential but challenges like lack of time, incentives, funding, standardization, and legal understanding exist. More tools, education, and training are needed for effective data sharing and an open science culture. Long-term effort is required for FAIR RDM.
CLINICAL RESEARCH IN CARDIOLOGY
(2023)
Article
Rheumatology
Bella Mehta, Susan Goodman, Edward DiCarlo, Deanna Jannat-Khah, J. Alex B. Gibbons, Miguel Otero, Laura Donlin, Tania Pannellini, William H. H. Robinson, Peter Sculco, Mark Figgie, Jose Rodriguez, Jessica M. M. Kirschmann, James Thompson, David Slater, Damon Frezza, Zhenxing Xu, Fei Wang, Dana E. E. Orange
Summary: This study aimed to differentiate osteoarthritis (OA) and rheumatoid arthritis (RA) by examining hematoxylin and eosin (H&E)-stained synovial tissue samples. OA patients exhibited increased mast cells and fibrosis, while RA patients showed increased lymphocytic inflammation, lining hyperplasia, neutrophils, detritus, plasma cells, binucleate plasma cells, sub-lining giant cells, fibrin, Russell bodies, and synovial lining giant cells. Combining pathologist scores with cell density metrics improved the classification accuracy.
ARTHRITIS RESEARCH & THERAPY
(2023)
Meeting Abstract
Rheumatology
Garrett Dunlap, Aaron Wagner, Nida Meednu, Anna Jonsson, Fan Zhang, Kevin Wei, Paul Utz, William Robinson, Holden Maecker, Judith James, Joel Guthridge, S. Louis Bridges, Laura Donlin, Susan Goodman, Edward DiCarlo, Vivian Bykerk, Christopher Ritchlin, Darren Tabechian, James Lederer, Ellen Gravallese, Mandy McGeachy, Gary S. Firestein, Peter Gregersen, Diane Horowitz, David Boyle, Laura Geraldino-Pardilla, Harris Perlman, Arthur Mandelin, Joan Bathon, Laura Hughes, V. Michael Holers, Kevin D. Deane, Larry Moreland, Andrew Filer, Costantino Pitzalis, Lindsy Forbess, Ami Ben-Artzi, Karen Salomon-Escoto, Soumya Raychaudhuri, Michael Brenner, Andrew McDavid, Jennifer Anolik, Deepak Rao
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Richard Bell, Matthew Brendel, Justin Xiang, Edward DiCarlo, Jennifer Anolik, Laura Donlin, Dana Orange, Edward Schwarz, Lionel Ivashkiv, Fei Wang
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Kartik Bhamidipati, Roopa Madhu, Sonia Presti, Youngmi Kim, Ye Cui, Fan Zhang, Anna Jonsson, Aparna Nathan, Nghia Millard, Deepak Rao, Laura Donlin, Jennifer Anolik, Soumya Raychaudhuri, Michael Brenner, Ilya Korsunsky, Kevin Wei
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Melanie Smith, Vianne Gao, Edward DiCarlo, Susan Goodman, Thomas Norman, Laura Donlin, Christina Leslie, Alexander Rudensky
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Juan Vargas, Nirmal Banda, Ian Mantel, Anna Jonsson, Kevin Wei, Deepak Rao, Susan Goodman, Kevin D. Deane, Jennifer Seifert, Jennifer Anolik, Michael Brenner, Soumya Raychaudhuri, Michael Holers, Laura Donlin, Fan Zhang
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Aaron Wagner, Nida Meednu, Garrett Dunlap, Fan Zhang, Anna Jonsson, Kevin Wei, Ami Ben-Artzi, Lindsy Forbess, Laura Geraldino-Pardilla, Diane Horowitz, Laura Hughes, Arthur Mandelin, Karen Salomon-Escoto, Darren Tabechian, Edward DiCarlo, Ellen Gravallese, Brendan Boyce, Christopher Ritchlin, James Lederer, Mandy McGeachy, Peter Gregersen, Paul Utz, William Robinson, Holden Maecker, Judith James, Joel Guthridge, Harris Perlman, Joan Bathon, Susan Goodman, Gary S. Firestein, David Boyle, S. Louis Bridges, Kevin D. Deane, V. Michael Holers, Larry Moreland, Andrew Filer, Costantino Pitzalis, Vivian Bykerk, Laura Donlin, Soumya Raychaudhuri, Michael Brenner, A. M. P. R. A. Lupus, Deepak Rao, Andrew McDavid, Jennifer Anolik
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Dana Weisenfeld, Fan Zhang, Laura Donlin, Anna Jonsson, William Apruzzese, Debbie Campbell, Ellen Gravallese, Larry Moreland, Susan Goodman, Michael Brenner, Soumya Raychaudhuri, Andrew Filer, Jennifer Anolik, Vivian Bykerk, Katherine Liao
ARTHRITIS & RHEUMATOLOGY
(2022)
Meeting Abstract
Rheumatology
Shady Younis, Orr Sharpe, Navin Rao, Julie Carman, Eddie James, Jane Buckner, Kevin D. Deane, Michael Holers, Laura Donlin, Mark Davis, William Robinson
ARTHRITIS & RHEUMATOLOGY
(2022)