Article
Cell Biology
Maram Ganaiem, Gidon Karmon, Yanina Ivashko-Pachima, Illana Gozes
Summary: By using CRISPR/Cas9 genome editing, researchers have found that different mutations in the ADNP gene lead to distinct phenotypes in neuroblastoma cells. The p.Pro403* mutation is associated with an increase in the number and length of neurites, while the p.Tyr718* mutation decreases cell numbers. These phenotypic differences are related to increased expression of the mutant proteins in the cytoplasm, and the p.Tyr718* mutation leads to reduced nuclear/cytoplasmic boundaries, which can be corrected by the ADNP-derived drug candidate NAP.
Article
Multidisciplinary Sciences
Chun-Hong Nie, Shi-Ming Wan, Yu-Long Chen, Ann Huysseune, Ya-Ming Wu, Jia-Jia Zhou, Alexandre Wagner Silva Hilsdorf, Wei-Min Wang, Paul Eckhard Witten, Qiang Lin, Ze-Xia Gao
Summary: IBs are mineralized spicules found in the myosepta of some teleost species. This study evaluated the characteristics of IB tissue using single-cell transcriptomics in zebrafish and identified 18 distinct cell types. The analysis showed that IBs are derived from tendons and that a core tendon-osteoblast cell lineage is related to IB formation. The researchers also identified 10 candidate genes and demonstrated the crucial role of runx2b regulation in IB formation. This research provides a genetic breeding strategy to generate commercial fish species without IBs, improving their safety and economic value.
NATIONAL SCIENCE REVIEW
(2022)
Article
Immunology
Miriam T. Kastlmeier, Erika Gonzalez-Rodriguez, Phoebe Cabanis, Eva M. Guenther, Ann-Christine Koenig, Lianyong Han, Stefanie M. Hauck, Fenja See, Sara Asgharpour, Christina Bukas, Gerald Burgstaller, Marie Piraud, Mareike Lehmann, Rudolf A. Hatz, Juergen Behr, Tobias Stoeger, Anne Hilgendorff, Carola Voss
Summary: Interstitial lung disease (ILD) is a diverse group of lung disorders characterized by persistent architectural distortion of the lung parenchyma. In this study, a 3D organoid co-culture model was developed to investigate the mesenchymal-epithelial crosstalk in ILD. The results showed that ILD fibroblasts increased metabolic activity and altered stem cell function in alveolar organoids.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Environmental Sciences
Kristin Doering, Claudia Ehlert, Katharina Pahnke, Martin Frank, Ralph Schneider, Patricia Grasse
Summary: The study compared the silicon isotope characteristics of different radiolarian taxa and sediment samples from different depths off the coast of Peru, revealing their relationship with dissolved silicic acid concentrations and providing insights into the potential use of radiolarian silicon isotopes in paleo reconstructions.
FRONTIERS IN MARINE SCIENCE
(2021)
Article
Oncology
Oren Yakovian, Julia Sajman, Rand Arafeh, Yair Neve-Oz, Michal Alon, Yardena Samuels, Eilon Sherman
Summary: The study reveals the nanoscale organization and signal coupling of NRas and BRAF in melanoma cells, showing that mutant NRas exhibits more pronounced self-clustering and increased association with BRAF. The findings suggest a new regulatory mechanism for NRas signaling and potential therapeutic targets for MEK inhibitors in melanoma.
Article
Biochemistry & Molecular Biology
Miguel A. A. Minaya, Sidhartha Mahali, Abhirami K. K. Iyer, Abdallah M. M. Eteleeb, Rita Martinez, Guangming Huang, John Budde, Sally Temple, Alissa L. L. Nana, William W. W. Seeley, Salvatore Spina, Lea T. T. Grinberg, Oscar Harari, Celeste M. M. Karch
Summary: This study aimed to determine the common molecular signature of frontotemporal lobar dementia. The results showed that MAPT mutations led to disruptions in calcium homeostasis, affecting synaptic and lysosomal function as well as neuronal development. Some of the commonly differentially expressed genes were also found in the brains of other tauopathy disorders. Therefore, induced pluripotent stem cell-derived neurons can be used to study the molecular mechanisms of frontotemporal lobar dementia.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Clinical Neurology
Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone
Summary: The study found that nEVs isolated from DS children showed a significant increase in insulin resistance marker pIRS1(Ser636) and hyperactivation of the Akt/mTOR/p70S6K pathway downstream from IRS1, possibly driven by higher inhibition of PTEN. Additionally, high levels of pGSK3 beta(Ser9) were also observed. These alterations in the insulin-signaling/mTOR pathways are believed to be early events in the DS brain, contributing to the cognitive dysfunction and intellectual disability seen in this unique population.
ALZHEIMERS & DEMENTIA
(2022)
Article
Biochemistry & Molecular Biology
Ragousandirane Radjasandirane, Alexandre G. de Brevern
Summary: Essential thrombocythemia (ET) is a blood cancer characterized by platelet overproduction. CALR mutations are found in 25-30% of ET patients, and JAK2, MPL, or CALR proteins may be involved in platelet overproduction. CALR variants are classified into five classes, with A and B being the most common in ET patients. Molecular dynamics simulations were used to analyze the structural dynamics of these five classes. The results suggest that the newly formed disulfide bond in classes A, B, and C may play an essential role in the pathogenicity of these variants, while class E is unrelated to ET and represents human polymorphisms.
Article
Immunology
Chuanqing Jing, Rong Fu, Xue Liu, Guodong Zang, Xue Zhu, Can Wang, Wei Zhang
Summary: This study identified three different cuproptosis patterns in patients with idiopathic pulmonary fibrosis (IPF) based on cuproptosis-related genes, and found significant differences in prognosis and immune characteristics among these patterns. The cuproptosis score and five gene signatures can serve as reliable references for diagnosis and prognosis of IPF.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell & Tissue Engineering
Dongsheng Cai, Xiaochen Wang, Yaxun Sun, Hangping Fan, Jingjun Zhou, Zongkuai Yang, Hangyuan Qiu, Jue Wang, Jun Su, Tingyu Gong, Chenyang Jiang, Ping Liang
Summary: Aberrant activation of Wnt/β-catenin signaling contributes to the pathogenesis of SCN5A-related BrS, suggesting it as a potential therapeutic target.
STEM CELL RESEARCH & THERAPY
(2023)
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
Cell & Tissue Engineering
Danni Zhou, Ying Tan, Xiaoling Liu, Ling Tang, Hao Wang, Jiaxi Shen, Wei Wang, Lenan Zhuang, Juan Tao, Jun Su, Tingyu Gong, Xiaorong Liu, Ping Liang, Feng Yu, Minghui Zhao
Summary: The study found that dysfunction of endothelial cells may be a central pathogenesis in atypical hemolytic uremic syndrome (aHUS), and using induced pluripotent stem cell-derived endothelial cell model can provide insights into the molecular mechanisms of the disease. The activation of the p38 MAPK signaling pathway could be a potential therapeutic target for aHUS treatment.
Article
Oncology
Wenna Jiang, Lu Qiao, Duo Zuo, Di Qin, Jiawei Xiao, Haohua An, Yanhui Wang, Xinwei Zhang, Yu Jin, Li Ren
Summary: The study revealed LDHA as an independent predictor of overall survival in pancreatic cancer patients, with significant alterations in patients' metabolites, including upregulation of lactic acid and downregulation of pyruvic acid. Combining different metabolite scores can effectively distinguish between pancreatic cancer patients and healthy controls.
ANNALS OF TRANSLATIONAL MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Al-Hassan M. Mustafa, Oliver H. Kramer
Summary: Janus kinase (JAK) signaling is a common drug target for human cancers. However, various mutant JAK molecules and drug resistance mechanisms limit the effectiveness of JAK inhibitors. Research has shown that epigenetic mechanisms, specifically histone deacetylases (HDAC), also play a role in controlling JAK-dependent signaling. Inhibitors of HDACs have been found to suppress oncogenic JAK-dependent signaling, providing new opportunities for cancer treatment.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Chengyu Wang, Tong Zhu, Zhangxiang Zhao, Bo Chen, Tingting Chen, Qi Dong, Mingyue Liu, Shuping Zhuang, Fan Yang, Yaoyao Liu, Min Yang, Yunyan Gu, Haihai Liang
Summary: The Hippo signaling pathway plays a crucial role in carcinogenesis, with downstream effector YAP1 being identified as potentially inhibiting CD8+ T cell infiltration in uterine corpus endometrial carcinoma by upregulating CREB1. Furthermore, esophageal carcinoma patients were classified into three subtypes based on a Hippo-immune gene panel, each with distinct characteristics in immune cell infiltration, immune pathways, and prognosis, suggesting a new classification of immune subtypes with prognostic implications in esophageal carcinoma.
Review
Biochemistry & Molecular Biology
William J. Valentine, Keisuke Yanagida, Hiroki Kawana, Nozomu Kono, Nobuo N. Noda, Junken Aoki, Hideo Shindou
Summary: The diversity of glycerophospholipid species in cellular membranes is immense and is influenced by the enzymes GPATs, LPLATs, and phospholipase A(1/2)s. In mammals, these enzymes play essential roles in physiology and disease processes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Haruka Chino, Akinori Yamasaki, Koji L. Ode, Hiroki R. Ueda, Nobuo N. Noda, Noboru Mizushima
Summary: This study reveals the critical role of LIR phosphorylation in the interaction, localization, and initiation of autophagy of the ER-phagy receptor TEX264 with ATG8. Structural analysis shows that phosphorylation increases binding affinity by generating multiple hydrogen bonds with ATG8, which cannot be mimicked by acidic residues. This finding highlights the importance of LIR phosphorylation in LIR-ATG8 interactions.
Article
Cell Biology
Takuo Osawa, Kazuaki Matoba, Nobuo N. Noda
Summary: This article summarizes the recent advances in the lipid transport activities of autophagy-related proteins and their collaboration mechanisms during autophagosome formation.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Article
Cell Biology
Sang-Won Park, Pureum Jeon, Akinori Yamasaki, Hye Eun Lee, Haneul Choi, Ji Young Mun, Yong-Woo Jun, Ju-Hui Park, Seung-Hwan Lee, Soo-Kyeong Lee, You-Kyung Lee, Hyun Kyu Song, Michael Lazarou, Dong-Hyong Cho, Masaaki Komatsu, Nobuo N. Noda, Deok-Jin Jang, Jin-A Lee
Summary: This study identified the selective interactions of various membrane-anchored mATG8 proteins in mammals and developed tools to regulate the autophagy of disease-related protein aggregates. This has significant implications for understanding the functional roles of mATG8 proteins on autophagic membranes in autophagy research.
Article
Chemistry, Multidisciplinary
Jin Cui, Yuta Ogasawara, Ikuko Kurata, Kazuaki Matoba, Yuko Fujioka, Nobuo N. Noda, Masakatsu Shibasaki, Takumi Watanabe
Summary: The study demonstrates that a stapled peptide derived from ATG16L1 exhibits potent binding affinity to ATG5, strong resistance to proteolysis, and significant autophagy inhibition activities in cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biophysics
Ashwini Patil
Summary: Intrinsically disordered regions in proteins play an important role in protein function, but the levels of intrinsic disorder vary in different proteins. Extensive research has shown that the levels of intrinsic disorder can vary across organisms, functions, diseases, and cellular locations. This review summarizes the known trends in the abundance of intrinsic disorder in groups of proteins under different conditions and functions, and presents new data on intrinsic disorder in cell type-specific proteins.
BIOPHYSICAL REVIEWS
(2022)
Review
Oncology
Yutaro Hama, Yuta Ogasawara, Nobuo N. Noda
Summary: Autophagy is a cellular process that degrades biomolecules and organelles, contributing to cellular homeostasis. Its roles in cancer are complex, acting as either a promoter or suppressor depending on the cancer stage and type. This review summarizes the basic mechanisms of autophagy and discusses its complicated roles in cancer. Additionally, it provides an overview of clinical trials on autophagy inhibitors for cancer and the development of more specific inhibitors for future clinical application.
Article
Biochemistry & Molecular Biology
Ryo Ikeda, Daisuke Noshiro, Hideaki Morishita, Shuhei Takada, Shun Kageyama, Yuko Fujioka, Tomoko Funakoshi, Satoko Komatsu-Hirota, Ritsuko Arai, Elena Ryzhii, Manabu Abe, Tomoaki Koga, Hozumi Motohashi, Mitsuyoshi Nakao, Kenji Sakimura, Arata Horii, Satoshi Waguri, Yoshinobu Ichimura, Nobuo N. Noda, Masaaki Komatsu
Summary: ULK1 is a kinase responsible for the phosphorylation of p62, which activates NRF2. p62(S351E/+) mice, with phosphorylation-mimicking mutation, exhibit NRF2 hyperactivation and growth retardation.
Editorial Material
Cell Biology
Tomoyuki Fukuda, Kentaro Furukawa, Tatsuro Maruyama, Nobuo N. Noda, Tomotake Kanki
Summary: Mitophagy is a selective form of autophagy that targets dysfunctional or superfluous mitochondria for degradation. Our recent study has identified Atg44 as a mitochondrial fission factor that generates mitochondrial fragments suitable for phagophore engulfment. We propose the term mitofissin to refer to Atg44 and its homologous proteins that might participate in diverse cellular processes.
Review
Biochemistry & Molecular Biology
Nobuo N. Noda
Summary: Autophagy is a conserved intracellular degradation system that involves the sequestration of degradation targets into autophagosomes. Autophagosome formation and cargo selectivity rely on core Atg proteins and cargo receptors, respectively. This review covers the 30-year history of structural studies on core Atg proteins and cargo receptors and discusses the molecular mechanisms of autophagosome formation and selective autophagy.
Article
Cell Biology
Kanae Hitomi, Tetsuya Kotani, Nobuo N. Noda, Yayoi Kimura, Hitoshi Nakatogawa
Summary: Hitomi et al. reveal that the phosphatidylinositol 3-kinase complex I is recruited to the autophagosome precursor via interactions with Vac8, Atg1 complex, and Atg9. These interactions cooperate to target the phosphatidylinositol 3-kinase complex I to the pre-autophagosomal structure and provide a molecular basis for its localization during autophagosome biogenesis.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ryosuke Ishimura, Sota Ito, Gaoxin Mao, Satoko Komatsu-Hirota, Toshifumi Inada, Nobuo N. Noda, Masaaki Komatsu
Summary: Research has shown that UFM1 plays a role in processes such as endoplasmic reticulum-associated protein degradation, ribosome-associated protein quality control, and ER-phagy, and the UFM1 E3 complex is involved in both ufmylation and ER-RQC.