Article
Oncology
Laura J. Jenkins, Ian Y. Luk, W. Douglas Fairlie, Erinna F. Lee, Michelle Palmieri, Kael L. Schoffer, Tao Tan, Irvin Ng, Natalia Vukelic, Sharon Tran, Janson W. T. Tse, Rebecca Nightingale, Zakia Alam, Fiona Chionh, George Iatropoulos, Matthias Ernst, Shoukat Afshar-Sterle, Jayesh Desai, Peter Gibbs, Oliver M. Sieber, Amardeep S. Dhillon, Niall C. Tebbutt, John M. Mariadason
Summary: The EGFR/RAS/MEK/ERK signaling pathway is hyperactivated in most colorectal cancers. Inhibitors of this pathway primarily induce cytostatic effects, but also induce expression of proapoptotic factors, suggesting they may prime colorectal cancer cells for apoptosis. Histone deacetylase inhibitors (HDACis) have the potential to synergize with ERK/MAPK inhibitors to trigger colorectal cancer cell apoptosis.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Cell Biology
Jinhuan Wu, Yuping Chen, Rui Li, Yaping Guan, Mu Chen, Hui Yin, Xiaoning Yang, Mingpeng Jin, Bingsong Huang, Xin Ding, Jie Yang, Zhe Wang, Yiming He, Qianwen Wang, Jian Luo, Ping Wang, Zhiyong Mao, Michael S. Y. Huen, Zhenkun Lou, Jian Yuan, Fanghua Gong
Summary: The study reveals that CDK2 regulates the ERK pathway through USP37, promoting cancer cell proliferation. Additionally, the combination of CDK1/2 and EGFR inhibitors shows a synergistic anticancer effect by reducing the stability and activity of ERK1/2.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Engineering, Biomedical
Catalina Pineda Molina, George S. Hussey, Alvin Liu, Jonas Eriksson, William A. D'Angelo, Stephen F. Badylak
Summary: The study suggests that surgical meshes composed of naturally occurring materials, such as 4HB, can increase resistance to surgical site infections by activating molecular pathways promoting antimicrobial peptide expression. The findings provide insights into the mechanisms behind the decreased incidence of infections associated with the use of these meshes.
Letter
Plant Sciences
Xiaojing Liu, Weijia Cheng, Peng Yao, Kexin Ren, Yu Wang, Yingnan Sun, Xin Hou, Li Lu, Xiangsong Chen
Summary: Conserved serine phosphorylation regulates histone deacetylase activity in Arabidopsis and humans.
Review
Biochemistry & Molecular Biology
Sonali Bahl, Edward Seto
Summary: Histone deacetylases (HDACs) are enzymes that regulate cellular processes by removing acetyl groups from proteins. HDAC activities are regulated by various mechanisms, including posttranslational modifications like reversible phosphorylation. Dysregulation of HDACs can contribute to disease development, making it important to understand how reversible phosphorylation affects their functions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Editorial Material
Hematology
Monika Haemmerle
Summary: This study explores the role of Mnk1 in megakaryocytes and platelets, showing that it regulates protein synthesis and affects megakaryocyte ploidy and platelet production. These findings have clinical implications and contribute to our understanding of platelet function and thrombosis.
Article
Chemistry, Medicinal
Xudong Liu, Jie Gao, Yaohui Sun, Feng Zhang, Wenzhi Guo, Shuijun Zhang
Summary: This study found that clotrimazole inhibits the migration and invasion of HCC cells by repressing ERK phosphorylation, involving EMT. This has important implications for the development of therapeutic strategies for HCC.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Chemistry, Multidisciplinary
Xiaosheng Tan, Changxing Qi, Xiangli Zhao, Lingjuan Sun, Mi Wu, Weiguang Sun, Lianghu Gu, Fengqing Wang, Hao Feng, Xia Huang, Bin Xie, Zhengyi Shi, Peiling Xie, Meng Wu, Yonghui Zhang, Gang Chen
Summary: This study reveals the importance of the extracellular regulated protein kinases (ERK) signaling pathway in the development of allograft rejection. By using a specific ERK inhibitor called lycorine, the researchers found that inhibition of ERK significantly prolongs allograft survival and decreases the number and activation of infiltrating T cells. Further analysis shows that lycorine-treated T cells exhibit mitochondrial dysfunction and metabolic reprogramming, resulting in reduced responsiveness to stimulation. Transcriptome analysis also reveals downregulated immune response, mitogen-activated protein kinase cascade, and metabolic processes in lycorine-treated T cells. These findings provide new insights into the development of immunosuppressive agents targeting the ERK pathway involved in T-cell activation and allograft rejection.
Article
Cell Biology
Hideyuki Nakashima, Keita Tsujimura, Koichiro Irie, Takuya Imamura, Cleber A. Trujillo, Masataka Ishizu, Masahiro Uesaka, Miao Pan, Hirofumi Noguchi, Kanako Okada, Kei Aoyagi, Tomoko Andoh-Noda, Hideyuki Okano, Alysson R. Muotri, Kinichi Nakashima
Summary: This study reveals the mechanism of MeCP2/miR-199a axis in regulating neural stem cell differentiation, further confirming the importance of BMP signaling in RTT brain development, and proposing the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.
Article
Cell Biology
Tsuyoshi Hirashima, Naoya Hino, Kazuhiro Aoki, Michiyuki Matsuda
Summary: This article reviews the critical regulatory role of extracellular signal-regulated kinase (ERK) in various physiological and pathological processes and highlights the signaling mechanisms governing ERK activation via biochemical regulations with upstream molecules, particularly receptor tyrosine kinases (RTKs). However, recent research has revealed the role of mechanical forces in activating the RTK-ERK signaling pathways, opening new avenues of research into mechanochemical interplay in multicellular tissues.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Article
Oncology
Elena Rampazzo, Lorenzo Manfreda, Silvia Bresolin, Alice Cani, Elena Mariotto, Roberta Bortolozzi, Alessandro Della Puppa, Giampietro Viola, Luca Persano
Summary: Glioblastoma is the deadliest brain tumor with limited treatment options. This study found that histone deacetylase inhibitors can suppress the aggressive features of the tumor, including stem cell characteristics, proliferation, and motility. These inhibitors show potential as therapeutic agents for glioblastoma.
Article
Chemistry, Medicinal
Marian N. Aziz, Linh Nguyen, Yan Chang, Delphine Gout, Zui Pan, Carl J. Lovely
Summary: The discovery of a new class of extracellular-signal-regulated kinase (ERK) inhibitors was achieved through the development of novel 2-imino-5-arylidene-thiazolidine analogues. These targeted thiazolidines were synthesized using a solid support-mediated reaction and showed good chemical and physical stability. The best compound among the synthesized library, (Z)-5-((Z)-4-bromobenzylidene)-N-(4-methoxy-2-nitrophenyl)-4,4-dimethylthiazolidin-2-imine (6g), demonstrated high selectivity in cell viability assays and selective inhibition of phosphorylation in the ERK pathway. Molecular modeling techniques confirmed the observed activity and suggested potential for the development of bioactive 2-imino-5-arylidene-thiazolidines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Kristen Kurtzeborn, Hyuk Nam Kwon, Vladislav Iaroshenko, Imrul Faisal, Martin Ambroz, Xing Jin, Talha Qureshi, Jussi Kupari, Anneliis Ihermann-Hella, Juho Vaananen, Henna Tyynismaa, Iva Bousova, Sunghyouk Park, Satu Kuure
Summary: Through RNA sequencing and tissue-specific MAPK/ERK inactivation experiments, we found that MAPK/ERK signaling maintains ureteric bud tip cells, potentially playing a regulatory role in collecting duct progenitors. Additionally, we provide new mechanistic insights on how MAPK/ERK signaling regulates progenitor maintenance through its effects on chromatin accessibility and energy metabolism.
Article
Cardiac & Cardiovascular Systems
Ting-Ting Zhang, Qing-Qing Lei, Jie He, Xin Guan, Xin Zhang, Ying Huang, Zi-Yue Zhou, Rui-Xin Fan, Ting Wang, Chen-Xi Li, Jin-Yan Shang, Zhuo-Miao Lin, Wan-Li Peng, Li-Kai Xia, Yu-Ling He, Chuan-Ying Hong, Jing-Song Ou, Rui-Ping Pang, Xiao-Ping Fan, Hui Huang, Jia-Guo Zhou
Summary: This study reveals that Best3 mutation, which mainly acts in blood vessels, leads to aortic dissection by regulating the degradation of MEKK2/3, controlling smooth muscle cell phenotypic switch, and maintaining the structural integrity of the aorta. This provides a new therapeutic target for the treatment of aortic dissection.
Article
Oncology
Danhui Liu, Yuzhen Liu, Bo Qi, Chengwei Gu, Shuhua Huo, Baosheng Zhao
Summary: Recent studies have shown that HDAC inhibitors promote cancer cell migration. However, inhibition of Slug or PAI-1 can reduce HDAC inhibitor-induced cancer cell migration. In addition, blocking ERK1/2 activation can also inhibit HDAC inhibitor-induced cancer cell migration.
Editorial Material
Cell Biology
Kirsten L. Bryant, Channing J. Der
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2019)
Retraction
Biochemistry & Molecular Biology
Pat P. Ongusaha, Hyung-Gu Kim, Sarah A. Boswell, Anne J. Ridley, Channing J. Der, G. Paolo Dotto, Young-Bum Kim, Stuart A. Aaronson, Sam W. Lee
Article
Biochemistry & Molecular Biology
Devon R. Blake, Angelina V. Vaseva, Richard G. Hodge, McKenzie P. Kline, Thomas S. K. Gilbert, Vikas Tyagi, Daowei Huang, Gabrielle C. Whiten, Jacob E. Larson, Xiaodong Wang, Kenneth H. Pearce, Laura E. Herring, Lee M. Graves, Stephen V. Frye, Michael J. Emanuele, Adrienne D. Cox, Channing J. Der
Editorial Material
Oncology
G. Aaron Hobbs, Channing J. Der
Article
Biochemistry & Molecular Biology
Hua Yang, Shengyan Xiang, Aslamuzzaman Kazi, Said M. Sebti
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Yao-Cheng Li, Nikki K. Lytle, Seth T. Gammon, Luke Wang, Tikvah K. Hayes, Margie N. Sutton, Robert C. Bast, Channing J. Der, David Piwnica-Worms, Frank McCormick, Geoffrey M. Wahl
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Biochemistry & Molecular Biology
Clint A. Stalnecker, Channing J. Der
Article
Cell Biology
Chen Hu, Mu Zhang, Niko Moses, Cong-li Hu, Lisa Polin, Wei Chen, Hyejeong Jang, Joshua Heyza, Agnes Malysa, Joseph A. Caruso, Shengyan Xiang, Steve Patrick, Paul Stemmer, Zhenkun Lou, Wenlong Bai, Chuangui Wang, Gerold Bepler, Xiaohong Mary Zhang
CELL DEATH & DISEASE
(2020)
Article
Cell Biology
Niko Moses, Mu Zhang, Jheng-Yu Wu, Chen Hu, Shengyan Xiang, Xinran Geng, Yue Chen, Wenlong Bai, You-Wei Zhang, Gerold Bepler, Xiaohong Mary Zhang
Review
Biochemistry & Molecular Biology
Jennifer E. Klomp, Jeff A. Klomp, Channing J. Der
Summary: The RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cascade is extensively studied and targeted by pharmaceutical industry. The ERK-MAPK cascade, initially thought to be a linear pathway, is now understood as a complex network with dynamic signaling inputs and outputs. Despite advances in understanding, the adaptability of cancer cells to inhibition of key nodes reveals a complexity that is not fully understood.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Oncology
Aslamuzzaman Kazi, Liwei Chen, Shengyan Xiang, Rajanikanth Vangipurapu, Hua Yang, Francisca Beato, Bin Fang, Terence M. Williams, Kazim Husain, Patrick Underwood, Jason B. Fleming, Mokenge Malafa, Eric A. Welsh, John Koomen, Jose Trevino, Said M. Sebti
Summary: The study revealed that the dependency of pancreatic cancer cells on mutant KRas is driven by the cyclin-dependent kinase (CDK) network, with knocking out CDK targets showing similar effects as knocking out KRas. The CDK inhibitor AT7519 was identified as a potent inducer of apoptosis in mutant KRas-dependent human cancer cells, demonstrating a link between CDK hyperactivation and mutant KRas dependency. This pharmacological approach was shown to effectively inhibit mutant KRas-driven pancreatic cancer in relevant models, suggesting potential for clinical investigations of AT7519 in patients with pancreatic cancer.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Wen-Hsuan Chang, Thuy-Tien Thi Nguyen, Chia-Hsin Hsu, Kirsten L. Bryant, Hong Jin Kim, Haoqiang Ying, Jon W. Erickson, Channing J. Der, Richard A. Cerione, Marc A. Antonyak
Summary: KRAS mutations lead to the production of exosomes enriched with the cell survival protein Survivin, which enhance cancer cell survival and resistance to chemotherapy drugs. Targeting Survivin within these exosomes could potentially serve as a therapeutic strategy for KRAS-dependent cancers.
Review
Biochemistry & Molecular Biology
Shengyan Xiang, Damon R. Reed, Mark G. Alexandrow
Summary: The CMG helicase is an important protein complex involved in DNA replication in mammalian cells. It plays a role in DNA melting and unwinding and is regulated by growth factors and signaling factors. Dysregulation of CMG can lead to genomic instability and contribute to tumorigenesis. This review aims to explore the regulation of CMG during its assembly and activation and highlights its potential as a therapeutic target in cancer.
Editorial Material
Oncology
Adrienne D. Cox, Jenny P. -Y. Ting, Channing J. Der
Summary: Hattori and colleagues developed drug-peptide conjugates using targeted small-molecule covalent inhibitors to generate cancer neoantigens, inducing an immune response against oncogene-mutant cancer cells. This immunotherapy strategy shows potential in overcoming treatment-induced resistance commonly observed in small molecule-based targeted anticancer drugs.