Article
Cell Biology
Thao Thi Dang, Mi-Jeong Kim, Yoon Young Lee, Hien Thi Le, Kook Hwan Kim, Somi Nam, Seung Hwa Hyun, Hong Lim Kim, Su Wol Chung, Hun Taeg Chung, Eek-Hoon Jho, Hiderou Yoshida, Kyoungmi Kim, Chan Young Park, Myung-Shik Lee, Sung Hoon Back
Summary: There are diverse links between macroautophagy/autophagy pathways and unfolded protein response (UPR) pathways under endoplasmic reticulum (ER) stress conditions. EIF2S1 phosphorylation plays an important role in regulating autophagy during ER stress by promoting nuclear translocation of TFEB and TFE3. Defects in EIF2S1 phosphorylation impair autophagic processes and hinder the restoration of ER homeostasis.
Article
Cell Biology
Enkhmaa Lkhagva-Yondon, Myeong Seong Seo, Yena Oh, Jonghun Jung, Eunhae Jeon, Kwangmin Na, Hyun Seung Yoo, Woo Chul Kim, Charlotte Esser, Sun U. Song, Myung-Shin Jeon
Summary: This study demonstrates that the aryl hydrocarbon receptor (AHR) plays a crucial role in regulating the immunosuppressive functions of mesenchymal stem cells (MSCs). The AHR deficiency leads to decreased expression of iNOS protein and impaired therapeutic efficacy of MSCs against graft-versus-host disease (GVHD). AHR controls the immunomodulatory functions of MSCs through ubiquitination of eEF2K, which affects iNOS protein synthesis and nitric oxide levels.
CELL DEATH & DISEASE
(2023)
Article
Neurosciences
Wen Lu, Kun Ni, Zhuangzhuang Li, Lili Xiao, Yini Li, Yumeng Jiang, Jincheng Zhang, Haibo Shi
Summary: This study revealed that salubrinal, a dephosphorylation inhibitor of eIF2 alpha signaling, can protect against cisplatin-induced damage in cochlear cells by attenuating endoplasmic reticulum stress. These findings suggest that pharmacological inhibition of eIF2 alpha-mediated ERS could be a potential treatment for cisplatin-induced ototoxicity.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Andrea Piserchio, Eta A. Isiorho, Kimberly Long, Amanda L. Bohanon, Eric A. Kumar, Nathan Will, David Jeruzalmi, Kevin N. Dalby, Ranajeet Ghose
Summary: Translation is a regulated process that maintains protein quality and adapts to energy/nutrient availability. eEF-2K, a key regulator of translation, phosphorylates eEF-2 to suppress the elongation phase of protein synthesis. Its activation requires calmodulin binding and phosphorylation at a specific site. The crystal structure of the eEF-2K and calmodulin complex reveals the atomic details of this activation mechanism.
Article
Cell Biology
Adam N. Keen, Luke A. Payne, Vedanta Mehta, Alistair Rice, Lisa J. Simpson, Kar Lai Pang, Armando del Rio Hernandez, John S. Reader, Ellie Tzima
Summary: Research reveals a noncanonical function of the protein synthesis component eIF6 in regulating cellular mechanobiology. Loss of eIF6 leads to reduced stiffness and force generation, accompanied by cytoskeletal and focal adhesion defects.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zheng Xiao-ci, Wu Die, Xu Xin
Summary: This article summarizes the research progress on the eIF2 alpha kinase family and its possible role in renal diseases, providing a new theoretical basis and reference for the prevention and treatment of kidney diseases.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Oncology
Hao-Xuan Du, Hu Wang, Xiao-Peng Ma, Hao Chen, Ai-Bin Dai, Ke-Xiang Zhu
Summary: Pancreatic cancer is a deadly disease with a poor prognosis, and immunotherapy has become a new focus in tumor treatment. This study investigates the potential of EIF2AK2 as a diagnostic and prognostic marker for pancreatic cancer by analyzing its expression and identifying differentially expressed genes. The results suggest that EIF2AK2 may serve as a biomarker for pancreatic cancer diagnosis and prognosis, as well as a potential therapeutic target.
Article
Multidisciplinary Sciences
Souradeep Basu, Jessica Greenwood, Andrew W. Jones, Paul Nurse
Summary: Cyclin-dependent kinases (CDKs) play a crucial role in eukaryotic cell cycle control, and the substrate specificities of S-CDKs and M-CDKs are remarkably similar, allowing S-CDK to carry out M-CDK functions under certain conditions.
Article
Cell Biology
Gaifen Li, Jia Liu, Mengyuan Guo, Yakun Gu, Yuying Guan, Qianqian Shao, Wei Ma, Xunming Ji
Summary: Chronic hypoxia leads to irreversible cognitive impairment, primarily due to hippocampal neurodegeneration. The underlying mechanism of this process is poorly understood. This study found that chronic hypoxia can induce alpha-synuclein hyperphosphorylation, protein aggregation, hippocampal neurodegeneration, and cognitive deficits. It was also discovered that chronic hypoxia enhances ceramide catabolism, leading to the inhibition of protein phosphatase 2A and sustained induction of alpha-synuclein hyperphosphorylation. Intermittent hypoxic preconditioning can protect against chronic hypoxia-induced hippocampal neurodegeneration and cognitive impairment by preventing alpha-synuclein hyperphosphorylation. This research reveals a novel mechanism underlying alpha-synuclein pathology during chronic hypoxia and has implications for developing therapeutic interventions for chronic hypoxia-related brain disorders.
CELL DEATH DISCOVERY
(2022)
Article
Oncology
Jeffrey R. White, Dakota T. Thompson, Kelsey E. Koch, Boris S. Kiriazov, Anna C. Beck, Dana M. van der Heide, Benjamin G. Grimm, Mikhail V. Kulak, Ronald J. Weigel
Summary: In melanoma metastasis, the role of the transcription factor AP-2 alpha is controversial, with some studies suggesting tumor suppressor activity while others show it facilitates metastasis by upregulating E2F pathway genes including EZH2. AP-2 alpha interacts with the NuRD complex, and its loss results in removal of activating chromatin marks and promotion of metastasis. These findings suggest AP-2 alpha can serve as a biomarker for predicting response to EZH2 inhibitors in treating advanced melanomas.
Article
Cell Biology
Junping Bao, Zhanyang Qian, Lei Liu, Xin Hong, Hui Che, Xiaotao Wu
Summary: The study reveals that the eIF2 alpha/ATF4/Ihh signaling pathway is involved in regulating ROS levels and apoptosis in NP cells, and disrupting this pathway may provide promising methods in preventing IDD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Emma Martinez-Alonso, Natalia Guerra-Perez, Alejandro Escobar-Peso, Lorena Peracho, Rocio Vera-Lechuga, Antonio Cruz-Culebras, Jaime Masjuan, Alberto Alcazar
Summary: This study investigates the role of protein translation regulation in ischemic stroke. The results demonstrate that the phosphorylation of eIF4G1 increases during ischemia-reperfusion, and it colocalizes with eIF4E in the vulnerable brain region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Irina Dobrescu, Elie Hammam, Jerzy M. Dziekan, Aurelie Claes, Ludovic Halby, Peter Preiser, Zbynek Bozdech, Paola B. Arimondo, Artur Scherf, Flore Nardella
Summary: Malaria drug resistance poses a challenge in treating the deadliest parasitic disease affecting millions worldwide. However, the development of quinoline-quinazoline-based inhibitors (compound 70) shows promise as new antimalarials. Through thermal proteome profiling (TPP), researchers discovered that eukaryotic translation initiation factor 3 (EIF3i) subunit I is the main target protein stabilized by compound 70 in Plasmodium falciparum. Further studies on PfEIF3i could lead to the design of new antimalarial drugs targeting the parasite's entire life cycle.
ACS INFECTIOUS DISEASES
(2023)
Article
Microbiology
Heather A. Walters, Brenda H. Welter, Harrison C. Moss, Martha A. Villano, Ronny Orobio-Hurtado, William J. Sullivan, Lesly A. Temesvari
Summary: This study identified two eIF2 alpha kinases in E. invadens that may regulate the stress response of Entamoeba, including oxidative stress, stage conversion, and virulence.
Article
Cell Biology
Christina Skofler, Florian Kleinegger, Stefanie Krassnig, Anna Maria Birkl-Toeglhofer, Georg Singer, Holger Till, Martin Benesch, Regina Cencic, John A. Porco, Jerry Pelletier, Christoph Castellani, Andrea Raicht, Ewa Izycka-Swieszewska, Piotr Czapiewski, Johannes Haybaeck
Summary: The study found that eIF4AI is overexpressed in NB patient tissue, and treatment with CR-1-31-B results in decreased viability, increased apoptosis rates, and changes in cell cycle distribution in NB cell lines. CR-1-31-B is effective against NB cell lines at low nanomolar doses and does not affect non-malignant cells.
Article
Biochemistry & Molecular Biology
Mitsuko Katsukawa, Shizue Ohsawa, Lina Zhang, Yan Yan, Tatsushi Igaki
Review
Cell Biology
Shizue Ohsawa, John Vaughen, Tatsushi Igaki
DEVELOPMENTAL CELL
(2018)
Article
Cell Biology
Rina Nagata, Mai Nakamura, Yuya Sanaki, Tatsushi Igaki
DEVELOPMENTAL CELL
(2019)
Article
Multidisciplinary Sciences
Chiaki Iida, Shizue Ohsawa, Kiichiro Taniguchi, Masatoshi Yamamoto, Gines Morata, Tatsushi Igaki
SCIENTIFIC REPORTS
(2019)
Article
Cell Biology
Yuya Sanaki, Rina Nagata, Daisuke Kizawa, Pierre Leopold, Tatsushi Igaki
DEVELOPMENTAL CELL
(2020)
Review
Oncology
Hiroshi Kanda, Tatsushi Igaki
Article
Developmental Biology
Yayoi Wada, Shizue Ohsawa, Tatsushi Igaki
Summary: The study on Drosophila mutants heterozygous for ribosomal protein genes revealed that deletion of the Hippo pathway effector yki resulted in severe wing growth defects, which were caused by JNK-mediated cell death signaling. The findings suggest a mechanism where tissues with reduced ribosomal proteins prevent ectopic apoptosis through Yki activity.
Article
Cell Biology
Masato Enomoto, Daisaku Takemoto, Tatsushi Igaki
Summary: The study found that in Drosophila imaginal epithelium, clones of Ras- or Src-activated benign tumors interact with each other to promote tumor malignancy. Ras-activated cells upregulate the ligand Delta, while Src-activated cells upregulate the receptor Notch, leading to Notch activation and upregulation of JAK-STAT signaling, ultimately resulting in tumor invasion.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Takao Ito, Tatsushi Igaki
Summary: The activation of Ras signaling induces cellular senescence, which must be overcome for cancer development. The ETS family transcriptional activator Pointed (Pnt) triggers cellular senescence and blocks Ras-induced tumor growth, revealing a mechanism of tumor progression involving microRNA-mediated inhibition of Pnt.
Article
Biochemistry & Molecular Biology
Rina Nagata, Nanami Akai, Shu Kondo, Kuniaki Saito, Shizue Ohsawa, Tatsushi Igaki
Summary: Mutations in the tumor-suppressor Hippo pathway activate the transcriptional coactivator Yorkie, leading to autonomous cell proliferation and non-autonomous cell death. This study reveals that Yki-induced supercompetition is crucial for tumorigenesis and is driven by non-autonomous induction of autophagy.
Article
Genetics & Heredity
Bojie Cong, Mai Nakamura, Yukari Sando, Takefumi Kondo, Shizue Ohsawa, Tatsushi Igaki
Summary: Identifying a common oncogenesis pathway among tumors with different oncogenic mutations is critical for developing anti-cancer strategies. Using fruit fly Drosophila as a model organism, researchers discovered a common oncogenesis pathway in malignant tumors and suppressed their growth using LAT1 inhibitors.