Article
Biochemistry & Molecular Biology
Shah Md. Toufiqur Rahman, Wenyuan Zhou, Alexander Deiters, Jason M. Haugh
Summary: Studying stress-activated signaling is challenging due to induced adaptation and imposed selection pressure. By using an optogenetic system to express light-activated p38 alpha or its upstream activator MKK6, the functional roles of these kinases in dynamic signaling programs are clarified.
Article
Medicine, Research & Experimental
Lulu Zhang, Chunmei Yang, Yanran Huang, Huakun Huang, Xiaohui Yuan, Ping Zhang, Caihong Ye, Mengqi Wei, Yuping Wang, Xiaoji Luo, Jinyong Luo
Summary: The study demonstrates that Cardamonin inhibits proliferation, migration, and invasion of osteosarcoma cells, inducing cell cycle arrest. It has minimal effects on normal cells and represses tumor growth in a xenograft mouse model. Mechanistically, Cardamonin activates the P38 and JNK MAPK signaling pathway to promote apoptosis in osteosarcoma cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Enkhtuya Radnaa, Lauren Richardson, Brett Goldman, Jared K. Burks, Tuvshintugs Baljinnyam, Natasha Vora, Hui-Juan Zhang, Elizabeth A. Bonney, Arum Han, Ramkumar Menon
Summary: This study investigated the impact of oxidative stress on p38 MAPK signaling and cell fate, using amnion epithelial cells. The results showed that excessive activation of p38 can have adverse effects on cell behavior and tissue homeostasis.
Article
Genetics & Heredity
Defu Lin, Huakang Du, Sen Zhao, Bowen Liu, Hongcheng Song, Guannan Wang, Weiping Zhang, Haiyan Liang, Pei Liu, Chao Liu, Wenwen Han, Zhenwu Li, Yang Yang, Shuofan Chen, Lina Zhao, Xiaoxin Li, Zhihong Wu, Ning Sun, Nan Wu
Summary: A novel BRAF variant was found to be associated with hypospadias phenotype, leading to abnormal p38 MAPK signaling. Two additional variants in p38 MAPK signaling-related genes were also identified potentially associated with hypospadias.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Pharmacology & Pharmacy
Nathalia Grave, Thamiris Becker Scheffel, Fernanda Fernandes Cruz, Liliana Rockenbach, Marcia Ines Goettert, Stefan Laufer, Fernanda Bueno Morrone
Summary: Gliomas are debilitating malignant brain tumors with limited response to therapies, driven by molecular abnormalities like mutations in regulatory networks. The MAPK pathway, particularly p38 MAPK activation, plays a crucial role in glioma cell invasion and metastasis, and is associated with tumor grade and chemotherapy resistance, underlining its potential as a therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Xiaochen Li, Xiaopei Cao, Hanqiu Zhao, Mingzhou Guo, Xiaoyu Fang, Ke Li, Lu Qin, Yuanzhou He, Xiansheng Liu
Summary: Hypoxia activates the Notch4-ERK/JNK/P38 MAPK signaling pathway to promote the proliferation, migration, and anti-apoptotic effects of LUAD cells. Notch4 plays a key role in the growth and metastasis of LUAD. Inhibitors of ERK, JNK, and P38 can partially reverse the effects of Notch4.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Hui Chen, Mindy Smith, Jasmin Herz, Tong Li, Rebecca Hasley, Cecile Le Saout, Ziang Zhu, Jie Cheng, Andres Gronda, Jose A. Martina, Pablo M. Irusta, Tatiana Karpova, Dorian B. McGavern, Marta Catalfamo
Summary: PAR1 activation in CD8 T cells accelerates calcium mobilization, facilitates granule trafficking through actin polymerization, and repositions the microtubule organizing center toward the immunological synapse. Mice lacking PAR1 exhibit reduced cytokine-producing T cells in response to viral infection, and specific deletion of PAR1 in LCMV GP33-specific CD8 T cells results in diminished expansion and effector function. These findings suggest that PAR1 plays a crucial role in T cell activation and function, offering a new therapeutic strategy to modulate CD8 T cell effector function.
Article
Genetics & Heredity
Taoruo Huang, Kota Suzuki, Hirofumi Kunitomo, Masahiro Tomioka, Yuichi Iino
Summary: Genetic analyses of C. elegans mutants reveal that the JNK and p38 signaling pathways play crucial roles in salt chemotaxis learning. These pathways may regulate neuropeptide signaling between sensory neurons and interneurons to promote high-salt chemotaxis after conditioning.
G3-GENES GENOMES GENETICS
(2023)
Article
Immunology
Dor Braverman, Jenia Gershberg, Neta Sal-Man
Summary: Enteropathogenic Escherichia coli (EPEC) is a major cause of gastrointestinal illness in developing countries. In this study, the researchers investigated the role of transmembrane domain (TMD) in the secretion and function of translocated intimin receptor (Tir) in host cells. They found that the C-terminal TMD (TMD2) is critical for Tir to escape integration into the bacterial membrane, while the N-terminal TMD (TMD1) is important for Tir's postsecretion function in host cells.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Biology
Yingyu Zhou, Tomohiro Takano, Xuyang Li, Yimei Wang, Rong Wang, Zhangliang Zhu, Masaru Tanokura, Takuya Miyakawa, Satoshi Hachimura
Summary: Beta-elemene regulates the balance of proinflammatory cytokines in mouse white adipose tissue through MAPK signaling, affecting the imbalance of M1-M2 macrophages and inhibiting the phosphorylation of MAPK pathways. These results suggest that beta-elemene may be a potential therapeutic medicine for macrophage-mediated chronic diseases.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tzu-Yu Hou, Shi-Bei Wu, Hui-Chuan Kau, Chieh-Chih Tsai
Summary: This study found that TGF-beta 1 induced myofibroblast transdifferentiation in human Graves' orbital fibroblasts through the p38 and JNK pathways, resulting in upregulation of CTGF, α-SMA, fibronectin, TIMP-1, and TIMP-3, while inhibiting the activities of MMP-2/-9.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Respiratory System
Mingzhou Guo, Mengzhe Zhang, Xiaopei Cao, Xiaoyu Fang, Ke Li, Lu Qin, Yuanzhou He, Jianping Zhao, Yongjian Xu, Xiansheng Liu, Xiaochen Li
Summary: This study reveals the important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling. Increased expression of Notch4 promotes proliferation and migration of HPASMCs and inhibits apoptosis through the ERK, JNK, and P38 signaling pathways. Silencing Notch4 partially alleviates the increase in RVSP and pulmonary vascular remodeling caused by hypoxia. These findings provide a potential therapeutic target for patients with HPH.
RESPIRATORY RESEARCH
(2022)
Article
Agronomy
Tingzhen Wang, Mingjia Liu, Yufeng Tian, Yingyan Han, Chaojie Liu, Jinghong Hao, Shuangxi Fan
Summary: This study investigates the important role of mitogen-activated protein kinase 6 (MAPK6) in high temperature bolting of lettuce. The researchers amplified the full-length coding sequence of the LsMAPK6 gene and analyzed its expression using real-time polymerase chain reaction. The results demonstrate that LsMAPK6 is mainly expressed in the stem, stem apex, and taproot, and its expression is significantly promoted by high temperatures.
Review
Gastroenterology & Hepatology
Benno Traub, Aileen Roth, Marko Kornmann, Uwe Knippschild, Joachim Bischof
Summary: Pancreatic cancer is a devastating disease with poor survival rates, prompting the need for new therapeutic approaches. Protein kinases play crucial roles in development and pathogenesis, making them potential targets for precision medicine in patients with deregulated kinase pathways.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Integrative & Complementary Medicine
Hu Xijiao, Li Shuoxi, Yang Dongxia, Gu Na, Liu Jinzhe, Wang Yawen, Liu Li, Sun Yiming
Summary: This study investigated the pharmacodynamic effects of modified Gexiazhuyu decoction (MGXZYD) and its underlying mechanism in the treatment of chronic salpingitis. The results showed that MGXZYD improved the pathological damage and fibrosis of the oviduct, decreased inflammation, and prevented the progression of chronic salpingitis by inhibiting the p38 MAPK signaling pathway.
JOURNAL OF TRADITIONAL CHINESE MEDICINE
(2022)
Article
Multidisciplinary Sciences
Mahima Sharma, James P. Lingford, Marija Petricevic, Alexander J. D. Snow, Yunyang Zhang, Michael A. Jarva, Janice W. -Y. Mui, Nichollas E. Scott, Eleanor C. Saunders, Ruwan Epa, Bruna M. da Silva, Douglas E. V. Pires, David B. Ascher, Malcolm J. McConville, Gideon J. Davies, Spencer J. Williams, Ethan D. Goddard-Borger
Summary: Degradation of sulfoquinovose is an important process in the carbon and sulfur cycles, allowing the utilization of the sugar's carbon skeleton. Agrobacterium tumefaciens imports sulfoquinovose and releases sulfite and glucose through oxidative desulfurization. This pathway is distributed among various bacterial orders and enables complete utilization of sulfoquinovose by a single organism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Paul D. Veith, Mikio Shoji, Nichollas E. Scott, Eric C. Reynolds
Summary: Porphyromonas gingivalis, an important human pathogen and model organism, has been shown to have O-glycosylation. This study identified 257 putative glycosylation sites in 145 glycoproteins and revealed the structure of the major O-glycan. The O-glycosylation system in P. gingivalis plays a role in establishing the physicochemical properties of the periplasm.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Chris Hadjineophytou, Jan Haug Anonsen, Tina Svingerud, Tatum D. Mortimer, Yonatan H. Grad, Nichollas E. Scott, Michael Koomey
Summary: Protein glycosylation systems in the genus Neisseria show species-specific variations, with different glycoprotein repertoires and target protein selection. The glycosylation of PilE, the pilin subunit of the type IV pilus colonization factor, is determined by the presence or absence of the PglO oligosaccharyltransferase in different species. This study highlights the importance of natural diversity in neisserial protein substrates and oligosaccharyltransferases in understanding the structure-function relationships of bacterial protein glycosylation systems.
Article
Microbiology
Clay D. Jackson-Litteken, Gisela Di Venanzio, Nguyen-Hung Le, Nichollas E. Scott, Bardya Djahanschiri, Jesus S. Distel, Evan J. Pardue, Ingo Ebersberger, Mario F. Feldman
Summary: Although pathogenic Acinetobacter can cause various infections, its importance as a uropathogen has been understudied. In this study, we identified a novel type II secretion system effector, InvL, that is essential for full uropathogenesis by a modern urinary isolate. InvL, with predicted structural similarity to the intimin-invasin family of autotransporter adhesins, is anchored to the membrane as a lipoprotein. However, similar to other invasin homologs, InvL functions as a bona fide adhesin, binding to extracellular matrix components and mediating adhesion to urinary tract cell lines. Overall, these findings establish InvL as an important adhesin for Acinetobacter's urinary tract virulence and represent the first report of a type II secretion system effector belonging to the intimin-invasin family.
Article
Multidisciplinary Sciences
Georgina L. Pollock, Andrey M. Grishin, Cristina Giogha, Jiyao Gan, Clare V. Oates, Paul J. McMillan, Isabella Gaeta, Matthew J. Tyska, Jaclyn S. Pearson, Nichollas E. Scott, Miroslaw Cygler, Elizabeth L. Hartland
Summary: Research reveals that during EPEC infection, NleH1 and NleH2 alter the cellular localization of Eps8 and the cytoskeletal composition of AE lesions by phosphorylating Ser775 of Eps8.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Sebastian A. Hughes, Meng Lin, Ashley Weir, Bing Huang, Liya Xiong, Ngee Kiat Chua, Jiyi Pang, Jascinta P. Santavanond, Rochelle Tixeira, Marcel Doerflinger, Yexuan Deng, Chien-Hsiung Yu, Natasha Silke, Stephanie A. Conos, Daniel Frank, Daniel S. Simpson, James M. Murphy, Kate E. Lawlor, Jaclyn S. Pearson, John Silke, Marc Pellegrini, Marco Herold, Ivan K. H. Poon, Seth L. Masters, Mingsong Li, Qin Tang, Yuxia Zhang, Maryam Rashidi, Lanlan Geng, James E. Vince
Summary: This study reveals that genetic mutations in X-linked inhibitor of apoptosis (XIAP) can lead to cell death-associated inflammatory diseases. The findings show that patients with XIAP deficiency-associated inflammatory bowel disease have increased inflammatory IL-1 beta maturation and cell death-associated caspase-8 and Gasdermin D (GSDMD) processing, which can be reduced by patient treatment.
Article
Biochemistry & Molecular Biology
Joel S. Bloch, Alan John, Runyu Mao, Somnath Mukherjee, Jeremy Boilevin, Rossitza N. Irobalieva, Tamis Darbre, Nichollas E. Scott, Jean-Louis Reymond, Anthony A. Kossiakoff, Ethan D. Goddard-Borger, Kaspar P. Locher
Summary: C-linked glycosylation is essential for the trafficking, folding, and function of secretory and transmembrane proteins involved in cellular communication processes. Cryogenic-electron microscopy structures of Caenorhabditis elegans CMT reveal how the CMT recognizes the glycosylation sequon and triggers conformational activation of the donor substrate, enabling C-glycosylation of proteins. These findings have implications for understanding human diseases and potential therapeutic targeting of specific CMT paralogs.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Microbiology
Benjamin P. Howden, Stefano G. Giulieri, Tania Wong Fok Lung, Sarah L. Baines, Liam K. Sharkey, Jean Y. H. Lee, Abderrahman Hachani, Ian R. Monk, Timothy P. Stinear
Summary: Invasive Staphylococcus aureus infections are common and often result in high mortality due to drug resistance. This review examines recent advances in understanding the interactions between S. aureus and its host, including immune responses, metabolism, and genomic plasticity. The authors also discuss the challenges in vaccine development and the role of other bacteria in shaping S. aureus colonization.
NATURE REVIEWS MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alan John, Stefanie M. Bader, Niccolay Madiedo Soler, Kharizta Wiradiputri, Swapnil Tichkule, Sean T. Smyth, Stuart A. Ralph, Aaron R. Jex, Nichollas E. Scott, Christopher J. Tonkin, Ethan D. Goddard-Borger
Summary: Cryptosporidium parvum is a common cause of diarrheal disease worldwide and developing vaccines to prevent or limit infection is important. The study investigates the architecture, conservation, and glycosylation of the CpTSP protein family in C. parvum. The results show that these proteins are modified with C-, O-, and N-linked glycans and are found on the cell surface and in secretory pathway-like structures. The study also reveals the presence of CpTSP1 in sporozoites and meronts, shedding new light on potential vaccine targets for cryptosporidiosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Jessica M. Lewis, Nichollas E. Scott
Summary: CRISPRi was used to investigate the effects of silencing O-linked glycosylation in four species of Burkholderia. The results showed that inducible silencing of PglL did not abolish glycosylation completely and did not lead to phenotypic changes or alterations in proteome associated with glycosylation null strains. In addition, high levels of rhamnose induction of CRISPRi had extensive impacts on the Burkholderia proteomes, making it difficult to determine the specific effects driven by CRISPRi guides without appropriate controls.
JOURNAL OF PROTEOME RESEARCH
(2023)
Review
Microbiology
Timesh D. Pillay, Sahampath U. Hettiarachchi, Jiyao Gan, Ines Diaz-Del-Olmo, Xiu-Jun Yu, Janina H. Muench, Teresa L. M. Thurston, Jaclyn S. Pearson
Summary: Salmonella injects numerous virulence factors into host cells, altering host cellular processes. These factors can mediate post-translational modifications of host proteins, impacting various cellular processes. Salmonella has provided valuable insight into bacterial pathogenesis, host signaling networks, and basic biochemistry. This review explores the host manipulation mediated by the Salmonella injectosome, focusing on post-translational modifications and their implications for infection outcomes, as well as highlighting poorly characterized effectors.
Article
Cell Biology
Kira L. Tomlinson, Ying-Tsun Chen, Alex Junker, AndreaCarola Urso, Tania Wong Fok Lung, Danielle Ahn, Casey E. Hofstaedter, Swikrity U. Baskota, Robert K. Ernst, Alice Prince, Sebastian A. Riquelme
Summary: Ketogenesis plays a role in shifting the immune response from inflammation to disease tolerance in pulmonary infection caused by Pseudomonas aeruginosa.
Article
Multidisciplinary Sciences
Mariana G. Sartorio, Evan J. Pardue, Nichollas E. Scott, Mario F. Feldman
Summary: Extracellular vesicles are produced in all three domains of life, and their biogenesis has common ancient origins in eukaryotes and archaea. Bacterial vesicles were discovered several decades ago, but there is skepticism about their biological relevance due to the lack of established biogenesis mechanisms. However, a study on Bacteroides thetaiotaomicron (Bt) showed that OMV production in bacteria is a highly regulated process, with OMVs playing key physiological roles through adaptation of their cargo for utilization of different polysaccharides.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Immunology
Thomas Naderer, Andre Mu, Andrew J. Monteith, Tania Wong Fok Lung
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)