Review
Developmental Biology
Akinobu Nakamura, Yuhei Goto, Yohei Kondo, Kazuhiro Aoki
Summary: This review provides an overview of the use of genetically encoded fluorescent biosensors for visualizing ERK activity in live cells, as well as their applications in developmental studies of model organisms. It discusses the current understanding of how ERK dynamics are encoded and decoded for cell fate decision-making.
Article
Cell Biology
Eunice Cho, Hua Jane Lou, Leena Kuruvilla, David A. Calderwood, Benjamin E. Turk
Summary: This study identifies PPP6C as a crucial phosphatase for MEK in the ERK pathway, which is frequently mutated or downregulated in melanoma. Loss of PPP6C leads to hyperphosphorylation of MEK, enhancing signaling through the pathway and reducing sensitivity to MEK inhibitors. Its recurrent mutations in melanoma cause MEK hyperphosphorylation, suggesting their role in promoting the disease by activating the core oncogenic pathway.
Article
Plant Sciences
Guowei Gong, Yuzhong Zheng, Xiangpeng Kong, Zhen Wen
Summary: Ononin, a bioactive compound found in functional foods or plants, has been shown to exhibit anticancer properties in both in vitro and in vivo studies. In this study, ononin was also found to inhibit endothelial cell angiogenesis and suppress tumor cell proliferation. The potential role of ononin as a candidate for prevention and treatment of angiogenesis-related diseases was highlighted in this research.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Cell Biology
Zhen-Yuan Zheng, Man-Yu Chu, Wan Lin, Ya-Qi Zheng, Xiu-E Xu, Yang Chen, Lian-Di Liao, Zhi-Yong Wu, Shao-Hong Wang, En-Min Li, Li-Yan Xu
Summary: In esophageal squamous cell carcinoma (ESCC), the MAPK signaling pathway is highly activated and associated with poor prognosis. Inhibiting MAPK leads to rapid activation of the STAT3 pathway. Combination therapy targeting both MAPK and STAT3 may be an effective strategy for ESCC treatment.
CELL DEATH & DISEASE
(2022)
Article
Plant Sciences
Yaqi Kang, Jing Lin, Long Wang, Xin Shen, Jingyan Li, Anguo Wu, Liang Yue, Liuping Wei, Yun Ye, Jing Yang, Jianming Wu
Summary: This study identifies Hirsutine as a potential treatment option for thrombocytopenia, as it promotes megakaryocytic differentiation and maturation through the MEK/ERK/FOG1/TAL1 signaling pathway.
Article
Multidisciplinary Sciences
Arnaud Landra-Willm, Ameya Karapurkar, Alexia Duveau, Anne Amandine Chassot, Lucille Esnault, Gerard Callejo, Marion Bied, Stephanie Hafner, Florian Lesage, Brigitte Wdziekonski, Anne Baron, Pascal Fossat, Laurent Marsollier, Xavier Gasull, Eric Boue-Grabot, Michael A. Kienzler, Guillaume Sandoz
Summary: By manipulating neuronal activity using optogenetics and photopharmacology, researchers have developed a light-activatable molecule called LAKI that can block pain-related potassium channels. This molecule has the potential to be a valuable tool for studying these channels, and it can also be used to remotely control pain in animal models without the need for genetic manipulations or viral infection. This non-invasive and reversible approach has applications in pain research and drug screening.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Kezhou Xia, Di Zheng, Zhun Wei, Wenda Liu, Weichun Guo
Summary: Recent studies have shown that TRIM26 gene is downregulated in osteosarcoma and higher expression of TRIM26 is associated with better prognosis. Overexpression of TRIM26 can promote the degradation of RACK1, leading to inactivation of MEK/ERK signaling and inhibition of osteosarcoma proliferation and invasion.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Wei Liu, Lei Wang, Jiajia Zhang, Kun Cheng, Wenming Zheng, Zhenling Ma
Summary: Ovarian cancer has a lower incidence rate compared to other gynecological tumor types, but it has the second-highest death rate. CCL2, a multifunctional factor associated with cancer progression, was found to promote proliferation and metastasis of ovarian cancer cells when overexpressed. Knocking down CCL2 inhibited ovarian cancer cell proliferation, migration, and invasion. The study showed that MAP3K19 is the key target through which CCL2 regulates ovarian cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chenyun Guo, Hao Xu, Yu Zhou, Zhihua Wu, Bin Jiang, Hanyu Chen, Donghai Lin
Summary: Cefotetan binds to hRKIP protein, relieving its inhibitory effect on the Ras/Raf1/MEK/ERK signaling pathway and enhancing ERK phosphorylation level. Several residues play a crucial role in the binding of hRKIP and Cefotetan. The binding of Cefotetan with hRKIP promotes protein motion, providing a basis for developing new drugs.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Koki Watanabe, Daiki Asano, Hiroko Ushikubo, Akane Morita, Asami Mori, Kenji Sakamoto, Kunio Ishii, Tsutomu Nakahara
Summary: Metformin can protect against NMDA-induced retinal neurotoxicity by activating the AMPK and MEK/ERK signaling pathways in rats. This neuroprotective effect may be partially due to inhibitory effects on inflammatory responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Yanlin Song, Zhenfei Bi, Yu Liu, Furong Qin, Yuquan Wei, Xiawei Wei
Summary: Molecular target inhibitors have been approved for tumor treatment and mainly target cell proliferation and metabolism. The RAS-RAF-MEK-ERK pathway plays essential roles in cell functions and abnormal activation of this pathway leads to tumor development. In this review, the development and potential combinations of inhibitors targeting this pathway are discussed.
Article
Biochemistry & Molecular Biology
Chuntian Huang, Ruijuan Du, Xuechao Jia, Kangdong Liu, Yan Qiao, Qiong Wu, Ning Yao, Lu Yang, Liting Zhou, Xuejiao Liu, Pu Xiang, Mingxia Xin, Yan Wang, Xiaojie Chen, Dong Joon Kim, Zigang Dong, Xiang Li
Summary: The study revealed that CDK15 plays a pivotal role in colorectal cancer progression by phosphorylating PAK4 to promote tumor growth. The CDK15-PAK4 axis may serve as a novel therapeutic target for colorectal cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Hui-Huang Lai, Liang-Yi Hung, Chia-Jui Yen, Hsu-Chin Hung, Ruo-Yu Chen, Yu-Chao Ku, Hang-Tat Lo, Hung-Wen Tsai, Yun-Ping Lee, Tz-Hsuan Yang, Yen-Yu Chen, Yi-Shuian Huang, Wenya Huang
Summary: The overexpression of DNA repair gene NEIL3 in hepatocellular carcinoma (HCC) is associated with tumor development and metastasis. NEIL3 activates specific pathways to promote epithelial-mesenchymal transition, leading to tumor resistance and metastasis. This study suggests that NEIL3 may serve as a potential biomarker for predicting HCC recurrence and clinical intervention.
JOURNAL OF PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Xinwei Liu, Jing Hao, Peng Wei, Xiaohong Zhao, Qiuyan Lan, Lu Ni, Yongzhen Chen, Xue Bai, Ling Ni, Chen Dong
Summary: In this study, the researchers found that SMAD4 plays a critical role in promoting CD8(+) T cell function in both tumor and infection models. SMAD4-mediated transcriptional regulation enhances CD8(+) T cell activation and cytotoxicity through the T cell receptor (TCR) signaling pathway. Furthermore, SMAD4 is directly phosphorylated by ERK following TCR activation.
Article
Oncology
Ye Song, Zhuo Li, Lei Li, Houming Zhou, Ting-Ting Zeng, Chuan Jin, Jin-Rong Lin, Sha Gao, Yan Li, Xin-Yuan Guan, Ying-Hui Zhu
Summary: The study identified SERPINA11 as a novel tumor suppressor in HCC, with the ability to inhibit cell growth, migration, and tumor metastasis. It has potential as a biomarker and intervention point for new therapeutic strategies in HCC.
JOURNAL OF HEPATOCELLULAR CARCINOMA
(2021)
Article
Multidisciplinary Sciences
Claire J. Weaver, Aleena L. Patel, Stanislav Y. Shvartsman, Michael S. Levine, Nicholas Treen
Summary: This study investigates the regulation of transcription factor condensates by ERK signaling in embryos of a simple proto-vertebrate. The authors demonstrate that ERK signaling induces changes in the localization of transcriptional repressor ERF and observe dynamic assembly and dissociation of condensates during interphase. These findings provide insights into the regulation of gene activity and cell signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Shannon E. Keenan, Maria Avdeeva, Liu Yang, Daniel S. Alber, Eric F. Wieschaus, Stanislav Y. Shvartsman
Summary: In this study, gene editing and microscopy were used to investigate the gene regulatory network involved in fruit fly embryonic development. A computational approach was developed to merge image data of individual components into a multivariable trajectory. The research revealed a low intrinsic dimensionality of posterior patterning and cell fate determination, allowing the construction of a model and predictions at the protein level.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biophysics
Jaspreet Singh, Jasmin Imran Alsous, Krishna Garikipati, Stanislav Y. Shvartsman
Summary: This article investigates the assembly process of intercellular bridges (ICBs) during cytokinesis, analyzing the mechanical properties of ICBs and the interplay between ring contraction and stiffening through experimental and theoretical models. The results reveal a dynamic competition between contractility and stiffening, with overlapping time intervals necessary for proper assembly of ICBs.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Robert A. Marmion, Alison G. Simpkins, Lena A. Barrett, David W. Denberg, Susan Zusman, Jodi Schottenfeld-Roames, Trudi Schupbach, Stanislav Y. Shvartsman
Summary: Germline mutations upregulating RAS signaling are associated with diverse developmental disorders. Utilizing controlled studies in Drosophila, researchers have discovered that activating variants of MEK, a core enzyme in the RAS pathway, cause phenotypic variations due to stochastic signaling variation. By quantifying cell fate specification errors, the study sheds light on the heterogeneity of developmental disorders caused by deregulated RAS signaling and provides a framework for investigating the effects of other pathogenic alleles and mild mutations.
Editorial Material
Cell Biology
Triveni Menon, Rebecca D. Burdine
Summary: The asymmetric expression of transcription factor Pitx2 is crucial for proper organ asymmetry during development. A recent study in Science reveals that Pitx2 expression, independent of Nodal, functions as a brake to counteract BMP4 signaling on the right side, leading to gut tilting.
DEVELOPMENTAL CELL
(2022)
Article
Chemistry, Multidisciplinary
Keonyong Lee, Kate Molloy O'Neill, Jayoung Ku, Stanislav Yefimovic Shvartsman, Yoosik Kim
Summary: The segmentation of the Drosophila embryo is regulated by localized maternal signals, including Bicoid and Nanos. The terminal system, controlled by mitogen-activated protein kinase, patterns the non-segmented termini. However, the spatial extent of this system in regulating gap genes beyond poles is unknown. Through study on mutagenized embryos, researchers discovered that the terminal system can establish multiple gene expression boundaries along the anteroposterior axis, displaying a potential bistability.
KOREAN JOURNAL OF CHEMICAL ENGINEERING
(2023)
Article
Health Care Sciences & Services
Nasreen Khan, Raquel D. Cabo, Rebecca Burdine, Wen-Hann J. Tan, Christopher Keary, Cesar M. Ochoa-Lubinoff, Lynne Bird, STARS Investigators
Summary: The purpose of this analysis is to study the quality of life, medical history, and medication use among individuals with Angelman syndrome (AS). The study used baseline data collected during a trial of gaboxadol (OV101) and found that AS has a significant impact on self-care, mobility, and daily activities. The study also showed that there is a high use of medications among AS patients.
QUALITY OF LIFE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Liyuan Zhu, Harold M. McNamara, Jared E. Toettcher
Summary: This article introduces a method for generating and screening a library of potential optogenetic tools directly in mammalian cells, and demonstrates its utility through the study of the Gal4-VP64 transcription factor.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Rocky Diegmiller, Jasmin Imran Alsous, Duojia Li, Yukiko M. Yamashita, Stanislav Y. Shvartsman
Summary: This study uses Drosophila melanogaster as a model to investigate the development of the shared organelle fusome in both male and female germline cysts. The findings reveal differences in the role and structure of the fusome between males and females, providing insights into the divergent outcomes of gametogenesis in different sexes. The study highlights the importance of quantitative measurements in biological sciences.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biology
Payam E. Farahani, Xiaoyu Yang, Emily Mesev, Kaylan A. Fomby, Ellen H. Brumbaugh-Reed, Caleb J. Bashor, Celeste M. Nelson, Jared E. Toettcher
Summary: pYtags is a modular approach for monitoring the activity of a specific RTK by live-cell microscopy. It enables monitoring of a specific RTK on different time and space scales with high specificity. Using pYtag biosensors, signaling dynamics can be quantitatively characterized with different activating ligands. The specificity and modularity of pYtags open the door to robust biosensors of multiple tyrosine kinases.
Article
Multidisciplinary Sciences
Victoria Patterson, Farid Ullah, Laura Bryant, John N. Griffin, Alpa Sidhu, Sheila Saliganan, Mackenzie Blaile, Margarita S. Saenz, Rosemarie Smith, Sara Ellingwood, Dorothy K. Grange, Xuyun Hu, Maimaiti Mireguli, Yanfei Luo, Yiping Shen, Maureen Mulhern, Elaine Zackai, Alyssa Ritter, Kosaki Izumi, Julia Hoefele, Matias Wagner, Korbinian M. Riedhammer, Barbara Seitz, Nathaniel H. Robin, Dana Goodloe, Cyril Mignot, Boris Keren, Helen Cox, Joanna Jarvis, Maja Hempel, Cynthia Forster Gibson, Frederic Tran Mau-Them, Antonio Vitobello, Ange-Line Bruel, Arthur Sorlin, Sarju Mehta, F. Lucy Raymond, Kelly Gilmore, Bradford C. Powell, Karen Weck, Chumei Li, Anneke T. Vulto-van Silfhout, Thea Giacomini, Maria Margherita Mancardi, Andrea Accogli, Vincenzo Salpietro, Federico Zara, Neeta L. Vora, Erica E. Davis, Rebecca Burdine, Elizabeth Bhoj
Summary: We report 21 families with neurodevelopmental differences and multiple congenital anomalies harboring rare variants in MAP4K4. Our study demonstrates that these variants are either loss-of-function or dominant-negative alleles, causing developmental defects. Furthermore, we show that MAP4K4 can restrain hyperactive RAS signaling in early embryonic stages. These findings establish MAP4K4 as a causal locus for individuals with syndromic neurodevelopmental differences.
Article
Developmental Biology
Emily K. Ho, Harrison R. Oatman, Sarah E. Mcfann, Liu Yang, Heath E. Johnson, Stanislav Y. Shvartsman, Jared E. Toettcher
Summary: This study investigates the formation of a gene expression stripe in early Drosophila embryos using optogenetics and live-cell biosensors. The research reveals the importance of ERK signaling dosage and time delay in the formation of the gene expression stripe. The findings provide valuable insights into the interpretation of developmental signals in both space and time.
Article
Biochemistry & Molecular Biology
Emily V. Mesev, Emma G. Guare, Alexander Ploss, Jared E. Toettcher
Summary: This study investigates the TYK2 dependency in type I and III interferon signaling using TYK2-deficient U2OS epithelial cells. The results show that TYK2 deficiency reduces signaling from both heterodimers of type I and III interferon receptors, while JAK1-associated homodimers are still fully competent in signaling independent of TYK2. The study suggests the involvement of noncanonical receptor complexes in TYK2-independent signaling downstream of type III interferon stimulation.
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Emily V. Mesev, Aaron E. Lin, Emma G. Guare, Brigitte L. Heller, Florian Douam, Britt Adamson, Jared E. Toettcher, Alexander Ploss
Summary: Interferons play crucial roles in antiviral defenses, and type I and III interferon receptors exhibit differences in signaling strength and dynamics. These differences are not due to ligand-binding affinity and receptor abundance, but are determined by specific regions within the intracellular domains of the receptors.