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
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
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
Dentistry, Oral Surgery & Medicine
Minmin Sun, Yaoting Ji, Shuhui Zhou, Rourong Chen, Hantao Yao, Minquan Du
Summary: This study demonstrates that ginsenoside Rb3 has the potential to inhibit osteoclastogenesis and attenuate gingivitis and alveolar bone resorption. Mechanistically, Rb3 achieves this by suppressing the activation of the ERK/NF-kappa B signaling pathway.
Article
Cell Biology
Mark D. Long, Justine J. Jacobi, Prashant K. Singh, Gerard Llimos, Sajad A. Wani, Aryn M. Rowsam, Spencer R. Rosario, Marlous Hoogstraat, Simon Linder, Jason Kirk, Hayley C. Affronti, Andries Bergman, Wilbert Zwart, Moray J. Campbell, Dominic J. Smiraglia
Summary: This study reveals the significant roles of NCOR2 in regulating prostate cancer progression, with reduced NCOR2 expression accelerating disease recurrence and inducing DNA hypermethylation. NCOR2 binds to specific transcription factors and regulates transcription in active enhancer regions.
Article
Chemistry, Medicinal
Debora Bublitz Anton, Julia Galvez Bulhoes Pedreira, Maria Luiza Zvirtes, Stefan A. Laufer, Rodrigo Gay Ducati, Marcia Goettert, Luis Fernando Saraiva Macedo Timmers
Summary: The SARS-CoV-2 virus has caused a global pandemic, infecting over 688 million people and resulting in around 6.8 million deaths. The virus induces lung inflammation and the release of pro-inflammatory cytokines, making anti-inflammatory therapies important in addition to antiviral drugs. The main protease (MPro) of SARS-CoV-2 is a potential drug target as it is essential for viral replication. In this study, six kinase inhibitors were evaluated for their inhibitory activity against SARS-CoV-2 MPro, and BIRB-796 and Baricitinib were identified as potential inhibitors with dual antiviral and anti-inflammatory activity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Immunology
Yuna Du, Huiqing Zhang, Yujie Guo, Kuangyu Song, Lifeng Zeng, Yiguo Chen, Zhengyu Xie, Rong Li
Summary: The study found that CD38(-/-) mice injected with Escherichia coli resulted in more severe pulmonary injuries and higher levels of cytokine mRNA expressions. CD38 deficiency increased the expressions of IL-1 beta and MCP-1 and aggravated pulmonary injury through the TLR4/ERK/NF-kB signaling pathway in sepsis.
MICROBES AND INFECTION
(2021)
Article
Cell Biology
Dongmei Zhang, Yunzhen Zhou, Yanan Ma, Ping Jiang, Hongchao Lv, Sijia Liu, Yu Mu, Chong Zhou, Shan Xiao, Guohua Ji, Peng Liu, Ning Zhang, Donglin Sun, Haiming Sun, Nan Wu, Yan Jin
Summary: In hepatocellular carcinoma (HCC), the overexpression of ribosomal protein L22-like1 (RPL22L1) is associated with malignancy and poor patient survival. RPL22L1 promotes cell proliferation, migration, invasion, and sorafenib resistance through activating ERK and inducing atypical epithelial-to-mesenchymal transition. The use of an ERK inhibitor enhances the efficacy of sorafenib in HCC patients with high RPL22L1 expression.
CELL DEATH DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Harikrishnareddy Paluvai, Kumar D. Shanmukha, Jens Tyedmers, Johannes Backs
Summary: Histone deacetylase 3 (HDAC3) and nuclear receptor co-repressor (NCoR1/2) are epigenetic regulators that play a key role in gene expression and metabolism. They are involved in the regulation of metabolic gene expression and their dysregulation has been associated with cardio-metabolic diseases, suggesting potential therapeutic interventions. More research is needed to understand the mechanisms through which HDAC3 and NCoR1/2 govern metabolic processes and their implications for treating metabolic diseases.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Microbiology
Chonglv Feng, Zhe Cheng, Zhijian Xu, Ye Tian, Huimin Tian, Fan Liu, Damin Luo, Yanhai Wang
Summary: This study describes the cell cycle regulation mechanism of germinative cells in the tapeworm Echinococcus multilocularis, which is influenced by the interaction between the parasite and the host. Host EGF regulates the G1/S phase of the cell cycle through the EGFR-ERK-EmCyclinD pathway.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Tsuyoshi Hirashima
Summary: This review explores the chemical and mechanical responses of cells during growth and development, leading to the formation of biological tissues. While the cell signaling mechanisms responsible for dynamic multicellular responses remain unclear, the extracellular signal-regulated kinase (ERK) pathway is discussed as a potential mechanism. Live imaging techniques for quantifying ERK activity in tissues are highlighted, along with their contribution to understanding tissue development and growth. The theoretical implications of ERK signaling are also discussed. Overall, this review provides insight into ERK-mediated multicellular responses and tissue morphogenesis.
BIOCHEMICAL JOURNAL
(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
Multidisciplinary Sciences
Avinash B. Patel, Jinkang Qing, Kelly H. Tam, Sara Zaman, Maria Luiso, Ishwar Radhakrishnan, Yuan He
Summary: The cryo-EM structure of the yeast Rpd3L HDAC complex is described, showing that key features are conserved in the human complex. The complex consists of two asymmetrically dimeric molecular assemblies, each containing copies of Sin3, Rpd3, and Ume1. The structure also reveals unexpected structural homology/analogy between unrelated subunits in fungal and mammalian complexes.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Jaime Gonzalez-Montero, Carlos I. Rojas, Mauricio Burotto
Summary: MAP4K4 is a serine/threonine kinase that plays a critical role in embryogenesis, cellular migration, and the development of metabolic diseases and cancer. Inhibiting MAP4K4 function has been shown to reduce tumor proliferation, migration, and invasion, making it a potential therapeutic target for various types of cancer. Specific MAP4K4 inhibitors have been developed but have not yet been tested in cancer patients.
FRONTIERS IN ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Nora Chouha, Hussein Abou-Hamdan, Hajime Yurugi, Riku Yoshii, Hiromi Ii, Ahmad Najem, Ghanem E. Ghanem, Susumu Nakata, Krishnaraj Rajalingam, Yu Peng, Dong Wang, Canan G. Nebigil, Laurent Desaubry
Summary: This study reports the structural requirements of fluorizoline analogues for their activities. Some compounds were found to have enhanced anti-C-RAF and anti-MEK activities, and higher cytotoxicity in HeLa cells compared to fluorizoline. These findings provide a foundation for further optimization of PHB ligands for cancer treatment and the discovery of a new chemical tool to study PHB signaling in cancers and other diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Karina A. Pena, Sofya Savransky, Breanna Lewis
Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu
Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu
Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou
Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin
Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera
Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban
Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen
Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
