Article
Biochemistry & Molecular Biology
Ruben Dario Castro-Torres, Jordi Olloquequi, Miren Etchetto, Pablo Caruana, Luke Steele, Kyra-Mae Leighton, Jesus Urena, Carlos Beas-Zarate, Antoni Camins, Ester Verdaguer, Carme Auladell
Summary: This study investigated the impact of dual genetic deletion of Mkk4/Mkk7 on hippocampal neurogenesis in adult mice. It was found that the levels of MKK4/MKK7 were not completely eliminated in the CNS after gene deletion, leading to alterations in hippocampal structure and maturation process. These data support the role of the MKK4/MKK7-JNK pathway in adult neurogenic activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Lei Gu, Xin He, Yanqiu Zhang, Shenglan Li, Jie Tang, Ruixue Ma, Xinyi Yang, Hao Huang, Yu Peng, Yanyun Xie, Zhangzhe Peng, Jie Meng, Gaoyun Hu, Lijian Tao, Xiaowei Liu
Summary: AKF-PD can protect against acute liver failure caused by acetaminophen or lipopolysaccharide/D-galactosamine, partially through regulating the MKK4/JNK pathway. It reduces necrosis, apoptosis, reactive oxygen species, and improves survival. It also shows protective effects in cell lines and primary hepatocytes. AKF-PD may be a novel candidate drug for acute liver failure.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Bo-Kyung Kim, Da-Mi Kim, Hyunkyung Park, Seon-Kyu Kim, Mi-Aie Hwang, Jungwoon Lee, Mi-Jung Kang, Jae-Eun Byun, Joo-Young Im, Minho Kang, Kyung Chan Park, Young Il Yeom, Seon-Young Kim, Haiyoung Jung, Dae-Hyuk Kweon, Jae-Ho Cheong, Misun Won
Summary: This study identified Synaptotagmin 11 (SYT11) as a potential therapeutic target and prognostic biomarker in gastric cancer (GC), particularly in the stem-like molecular subtype. SYT11 was found to promote epithelial-mesenchymal transition (EMT) and affect tumor proliferation and metastasis by activating the JNK signaling pathway. Additionally, SYT11 was identified as a potential prognostic biomarker for diffuse-type GC. These findings suggest the potential value of SYT11 as a therapeutic target and prognostic indicator in GC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Plant Sciences
Shengnan Li, Chao Cong, Yang Liu, Xiaofei Liu, Huicong Liu, Li Zhao, Xianwei Gao, Wenjia Gui, Lianwei Xu
Summary: Tiao Geng (TG) decoction, a Chinese herbal medicine extract, has been used for treating menopausal symptoms for over 30 years. The study showed that TG decoction inhibited TBTC-induced GT1-7 cell apoptosis through suppressing the ASK1/MKK7/JNK pathway, indicating its neuroprotective effect.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Immunology
Jian Wu, Feng-Ling Luo, Yan Xie, Huan Xiong, Yadong Gao, Guanghui Liu, Xiao-Lian Zhang
Summary: This study found that the secreted protein EST12, encoded by virulent Mycobacterium tuberculosis (M.tb) H37Rv region of deletion (RD)3, can regulate Myc expression and enhance the anti-mycobacterial immune response. EST12 activates the JNK-AP1-Myc pathway, leading to the production of pro-inflammatory cytokines and nitric oxide, which contributes to mycobacterial clearance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Le-le Liu, Yu Han, Zi-jia Zhang, Yi-qi Wang, Yu-wei Hu, Elena Kaznacheyeva, Jian-qing Ding, Dong-kai Guo, Guang-hui Wang, Bin Li, Hai-gang Ren
Summary: Parkinson's disease is a neurodegenerative motor disorder characterized by reduced dopamine levels. The loss of DJ-1 function leads to increased expression of MAO-B, which is associated with dopamine degradation, oxidative stress, and mitochondrial dysfunction. This study reveals the mechanistic link between DJ-1 and MAO-B expression and contributes to understanding the pathogenesis of Parkinson's disease.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Plant Sciences
Meiling Yuan, Yun Zhang, Lei Wang, Yaping Hua, Yan Wang, Hui Cheng, Ning Wang, Guangyun Wang, Saiwang Seto
Summary: This study demonstrates the protective effects of Tong-Qiao-Huo-Xue-Decoction (TQHXD) against cerebral ischemia-reperfusion (I/R) injury. By controlling the ASK1/MKK4/JNK pathway, TQHXD protects neurons from I/R damage and prevents apoptosis, providing a potential treatment for ischemic stroke.
Article
Oncology
Cong Xu, Yi-Ming Li, Bo Sun, Fang-Jing Zhong, Lian-Yue Yang
Summary: This study revealed that decreased expression of GNA14 was associated with aggressive features in hepatocellular carcinoma (HCC), while high expression was linked to better overall and disease-free survival. GNA14 acted as a suppressor inhibiting liver cancer progression through MAPK/JNK and PI3K/AKT signaling pathways.
Article
Cell Biology
Hao Yao, Yu Gao, Jiahui Han, Yan Wang, Jimin Cai, Yongjun Rui, Xin Ge
Summary: MKK4 can suppress oxidative stress and apoptosis and improve mitochondrial function in the liver upon hemorrhagic shock by inhibiting the JNK pathway. The MKK4/JNK axis is a therapeutic target for hemorrhagic shock-induced liver injury.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Cell Biology
Xiaohui Hua, Daimin Xiang, Mengxin Guo, Xiaohui Qian, Ruifan Chen, Tengda Li, Zhongxian Tian, Jiheng Xu, Chao Huang, Qipeng Xie, Chuanshu Huang
Summary: In this study, it was discovered that isorhapontigenin (ISO) initiates autophagic responses and inhibits bladder cancer (BC) invasion by activating the RAC1 protein translation and MKK7/JNK phosphorylation. The inhibition of autophagy was found to be crucial for ISO's inhibition of BC invasion. Mechanistic studies revealed that ISO inhibits miR-365a transcription, leading to upregulation of RAC1 translation, through the Dicer/miR145/SOX2/miR365a/RAC1 cascade, which in turn activates MKK7/JNK and induces autophagy.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Jing Lu, Xiaolei Tang, Dongmei Zhang, Tianye Lan, Qingxia Huang, Peng Xu, Miao Liu, Li Liu, Jian Wang
Summary: Based on network pharmacology and experimental validation, this study suggests that Didang tang (DDT) may treat intracerebral hemorrhage (ICH) by influencing the MAPK and apoptotic signaling pathways. In vitro and in vivo experiments confirmed the inhibitory effect of DDT on apoptosis and its ability to increase Bcl-2 expression, while suppressing the expression of certain core proteins.
Review
Biochemistry & Molecular Biology
Leon Katzengruber, Pascal Sander, Stefan Laufer
Summary: MKK4 is a dual-specificity protein kinase that regulates JNK and p38 MAPK signaling pathways, impacting cell proliferation, differentiation, and apoptosis. It is overexpressed in aggressive cancer types and plays a key role in liver regeneration. MKK4 is a promising target for cancer therapeutics and the treatment of liver-associated diseases. Recent progress in MKK4 drug discovery and the interest from a startup company highlight its importance in drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Shanshan Li, Jiayu Li, Ziwei Zhao, Sijia Xiao, Xiuping Shen, Xu Li, Xianpeng Zu, Xian Li, Yunheng Shen
Summary: The study demonstrates that Delavatine A (DA) has a protective effect on oxygen and glucose deprivation/reperfusion (OGD/R) injured neuronal cells and can alleviate brain ischemia/reperfusion (I/R) damage in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. This neuroprotection might be attributed to the suppression of the MKK7/JNK signaling pathway.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Chemistry, Medicinal
Paul Gehrtz, Shir Marom, Mike Buehrmann, Julia Hardick, Silke Kleinboelting, Amit Shraga, Christian Dubiella, Ronen Gabizon, Jan N. Wiese, Matthias P. Mueller, Galit Cohen, Ilana Babaev, Khriesto Shurrush, Liat Avram, Efrat Resnick, Haim Barr, Daniel Rauh, Nir London
Summary: High-throughput nanomole-scale synthesis allows for efficient and economical late-stage functionalization of compounds. Copper-catalyzed azide-alkyne cycloaddition has been demonstrated to be capable of nanoscale late-stage functionalization of covalent kinase inhibitors, enabling the synthesis of hundreds of compounds that do not require purification for biological assay screening. This study presents a promising approach to improving the properties of lead chemical matter through high-throughput late-stage functionalization of covalent inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Microbiology
Chao Yang, Qingwei Zuo, Xiao Liu, Qian Zhao, Haoyu Pu, Libo Gao, Lianfeng Zhao, Zhigang Guo, Yingbo Lin, Jianping Liu, Junlong Bi, Gefen Yin
Summary: The study identified cepharanthine as a potent inhibitor of PRRSV infection by suppressing the expression of multiple proteins and the NF-?B signaling pathway. This inhibition effectively reduced infection levels and protected cells from PRRSV invasion, suggesting CEP as a promising drug for PRRS control in veterinary clinics.
VETERINARY MICROBIOLOGY
(2021)
Editorial Material
Cell Biology
Hyungsoo Kim, Ze'ev A. Ronai
JOURNAL OF CELL BIOLOGY
(2018)
Article
Immunology
Honyin Chiu, Leandra V. Jackson, Kwon Ik Oh, Annie Mai, Ze'ev A. Ronai, Davide Ruggero, David A. Fruman
JOURNAL OF IMMUNOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Yu Fujita, Roberto Tinoco, Yan Li, Daniela Senft, Ze'ev A. Ronai
TRENDS IN MOLECULAR MEDICINE
(2019)
Article
Oncology
Yongmei Feng, E. Hampton Sessions, Fan Zhang, Fuqiang Ban, Veronica Placencio-Hickok, Chen-Ting Ma, Fu-Yue Zeng, Ian Pass, David B. Terry, Gregory Cadwell, Laurie A. Bankston, Robert C. Liddington, Thomas D. Y. Chung, Anthony B. Pinkerton, Eduard Sergienko, Martin Gleave, Neil A. Bhowmick, Michael R. Jackson, Artem Cherkasov, Ze'ev A. Ronai
Article
Multidisciplinary Sciences
Yan Li, Roberto Tinoco, Lisa Elmen, Igor Segota, Yibo Xian, Yu Fujita, Avinash Sahu, Raphy Zarecki, Kerrie Marie, Yongmei Feng, Ali Khateb, Dennie T. Frederick, Shiri K. Ashkenazi, Hyungsoo Kim, Eva Guijarro Perez, Chi-Ping Day, Rafael S. Segura Munoz, Robert Schmaltz, Shibu Yooseph, Miguel A. Tam, Tongwu Zhang, Emily Avitan-Hersh, Lihi Tzur, Shoshana Roizman, Ilanit Boyango, Gil Bar-Sela, Amir Orian, Randal J. Kaufman, Marcus Bosenberg, Colin R. Goding, Bas Baaten, Mitchell P. Levesque, Reinhard Dummer, Kevin Brown, Glenn Merlino, Eytan Ruppin, Keith Flaherty, Amanda Ramer-Tait, Tao Long, Scott N. Peterson, Linda M. Bradley, Ze'ev A. Ronai
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Tian-Xia Jiang, Jiang-Bo Zou, Qian-Qian Zhu, Cui Hua Liu, Guang-Fei Wang, Ting-Ting Du, Zi-Yu Luo, Fang Guo, Lu-Ming Zhou, Juan-Juan Liu, Wensheng Zhang, You-Sheng Shu, Li Yu, Peng Li, Ze'ev A. Ronai, Shu-ichi Matsuzawa, Alfred L. Goldberg, Xiao-Bo Qiu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Cell Biology
Gaurav Pathria, Joo Sang Lee, Erez Hasnis, Kristofferson Tandoc, David A. Scott, Sachin Verma, Yongmei Feng, Lionel Larue, Avinash D. Sahu, Ivan Topisirovic, Eytan Ruppin, Ze'ev A. Ronai
NATURE CELL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Marzia Scortegagna, Kathryn Hockemeyer, Igor Dolgalev, Joanna Pozniak, Florian Rambow, Yan Li, Yongmei Feng, Roberto Tinoco, Dennis C. Otero, Tongwu Zhang, Kevin Brown, Marcus Bosenberg, Linda M. Bradley, Jean-Christophe Marine, Ioannis Aifantis, Ze'ev A. Ronai
NATURE COMMUNICATIONS
(2020)
Review
Neurosciences
Scott N. Peterson, Linda M. Bradley, Ze'ev A. Ronai
CURRENT OPINION IN NEUROBIOLOGY
(2020)
Article
Cell Biology
Hyungsoo Kim, Heejung Kim, Yongmei Feng, Yan Li, Hironari Tamiya, Stefania Tocci, Ze'ev A. Ronai
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Gaurav Pathria, Sachin Verma, Jun Yin, David A. Scott, Ze'ev A. Ronai
Summary: Amino acid restriction is a promising cancer treatment strategy, but cancer cells develop mechanisms to resist this restriction. In melanoma cells with high asparagine levels, MAPK signaling activation impairs c-MYC degradation, leading to elevated c-MYC levels and enhanced ATF4 activation. Inhibiting the MAPK-c-MYC-SLC7A5 signaling axis can effectively suppress melanoma cell proliferation in combination with asparagine restriction.
Article
Oncology
Yongmei Feng, Gaurav Pathria, Susanne Heynen-Genel, Michael Jackson, Brian James, Jun Yin, David A. Scott, Ze'ev A. Ronai
Summary: IMD-0354, a potent inhibitor of glutamine uptake, demonstrated significant effects on melanoma cell growth, inducing cell cycle arrest, autophagy, and apoptosis. The drug showed pronounced effects in various tumor cell lines compared to non-transformed cells, highlighting its potential as a therapeutic and experimental tool that warrants further exploration.
MOLECULAR CANCER THERAPEUTICS
(2021)
News Item
Biochemistry & Molecular Biology
Ali Khateb, Ze'ev A. Ronai
Summary: The study reveals the important role of PKM2 as a pyruvate kinase in regulating cancer cell cholesterol metabolism, demonstrating its diverse tissue-specific functions and potential implications for cancer treatment.
Article
Oncology
Marzia Scortegagna, Yuanning Du, Linda M. Bradley, Kun Wang, Alfredo Molinolo, Eytan Ruppin, Rabi Murad, Ze'ev A. Ronai
Summary: Cellular components, such as myeloid cells, in the tumor microenvironment have significant impact on the progression and treatment response of lung adenocarcinoma (LUAD). This study reveals that the ubiquitin ligases Siah1a/2 regulate the differentiation and activity of alveolar macrophages (AM), and their control of AMs influences carcinogen-induced LUAD. The findings indicate that Siah1a/2 in AMs act as gatekeepers of lung cancer development by controlling inflammatory signaling, differentiation, and profibrotic phenotypes.
Review
Oncology
Daniela Senft, Jianfei Qi, Ze'ev A. Ronai
NATURE REVIEWS CANCER
(2018)
Article
Biochemistry & Molecular Biology
Kun He, Mengyi Xie, Weifeng Hong, Yonghe Li, Yaolin Yin, Xiaojin Gao, Yi He, Yu Chen, Chuan You, Jingdong Li
Summary: Centromere protein L (CENPL) is overexpressed in hepatocellular carcinoma (HCC) and is associated with poor patient prognosis. Upregulation of CENPL promotes tumor proliferation and glycolysis in HCC cells by activating the MEK1/2-ERK1/2 signaling pathway.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Yingzi Wang, Haozhong Huang, Huimin Weng, Chunsen Jia, Bin Liao, Yang Long, Fengxu Yu, Yongmei Nie
Summary: Talin protein plays a crucial role in transmitting mechanical forces by connecting the extracellular matrix to the cytoskeleton. It converts mechanical signals into biochemical signals and serves as diagnostic, therapeutic, and prognostic indicators in diseases.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Review
Biochemistry & Molecular Biology
Hema Saranya Ilamathi, Marc Germain
Summary: Mitochondria are the central metabolic hubs in cells, relying on proteins encoded by nuclear DNA and mitochondrial DNA (mtDNA) for their function. The maintenance and distribution of mtDNA are crucial for proper mitochondrial function and are associated with mitochondrial diseases. mtDNA is organized into nucleoids that dynamically move and interact with each other. The replication and distribution of mtDNA nucleoids are regulated by the complex interplay of mitochondrial dynamics, ER-mitochondria contact sites, and cytoskeletal networks.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
K. K. Sruthi, Sirisha Natani, Ramesh Ummanni
Summary: The overexpression of TPD52 is associated with the emergence of neuroendocrine prostate cancer (NEPC). TPD52 activates the NF-kappa B - STAT3 axis to induce neuroendocrine differentiation (NED) of prostate cancer cells. Therapeutic targeting of TPD52 is important for the treatment of prostate cancer.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
Article
Biochemistry & Molecular Biology
Cui Li, Feifan Xiang, Yuqi Gong, Yi Fu, Ge Chen, Zhi Wang, Zhong Li, Daiqing Wei
Summary: Our study demonstrates the significant role of tumor-derived microparticles (T-MPs) in osteosarcoma metastasis and immune response. T-MPs promote macrophage polarization and stimulate migration and chemoresistance of osteosarcoma cells, thereby affecting the progression of osteosarcoma.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2024)
