Article
Biochemistry & Molecular Biology
Ai Kaiho-Soma, Yoshino Akizuki, Katsuhide Igarashi, Akinori Endo, Takuji Shoda, Yasuko Kawase, Yosuke Demizu, Mikihiko Naito, Yasushi Saeki, Keiji Tanaka, Fumiaki Ohtake
Summary: The study reveals that the ubiquitin ligase TRIP12 and K29/K48-branched ubiquitin chains play crucial roles in targeted protein degradation, accelerating the degradation process induced by PROTACs. This cooperative mechanism is unique and enhances the efficiency of degrading neo-substrates.
Editorial Material
Biochemistry & Molecular Biology
Charlene M. Magtoto, Rebecca Feltham
Summary: The study demonstrates that the HECT-type E3 ubiquitin ligase TRIP12 cooperates with CRL complexes to promote PROTAC-induced degradation of neo-substrates by generating K29/K48-branched ubiquitin chains.
Article
Microbiology
Wei Zhang, Qi Wang, Fan Yang, Zixiang Zhu, Yueyue Duan, Yang Yang, Weijun Cao, Keshan Zhang, Junwu Ma, Xiangtao Liu, Haixue Zheng
Summary: JMJD6 is identified as a negative regulator of host innate immune responses to cytosolic viral RNA, reducing interferon production and impairing viral replication. It functions by promoting the ubiquitination degradation of IRF3 in RNF5-dependent manner to downregulate RLRs-mediated inflammatory responses.
Article
Cell Biology
Tiejian Nie, Kai Tao, Lin Zhu, Lu Huang, Sijun Hu, Ruixin Yang, Pingyi Xu, Zixu Mao, Qian Yang
Summary: This study demonstrates the critical role of chaperone-mediated autophagy (CMA) in maintaining proper mitochondria dynamics. Loss of this regulatory control may occur in Parkinson's disease (PD), leading to impaired mitochondria function. Increasing CMA activity promotes MARCHF5 turnover, reduces mitochondria fragmentation, and alleviates mitochondrial dysfunction under oxidative stress.
Article
Virology
Jing-Ping Huang, Ya-Xian Yang, Tian Chen, Dan-Dan Wang, Jing Li, Liang-Guo Xu
Summary: In this study, TRAF7 was identified as a negative regulator of innate immune signaling. TRAF7 interacts with TBK1 and promotes K48-linked polyubiquitination and degradation of TBK1 through its RING domain, impairing the activation of IRF3 and the production of IFN-β.
Article
Multidisciplinary Sciences
Rong Cai, Jiayu Ren, Mengyu Guo, Taotao Wei, Ying Liu, Chunyu Xie, Peng Zhang, Zhiling Guo, Andrew J. Chetwynd, Pu Chun Ke, Iseult Lynch, Chunying Chen
Summary: The nanomaterial-protein corona plays a crucial role in the cellular uptake and subcellular distribution of nanomaterials. Understanding its biological and toxicological characteristics is essential for the development of nanomedicine and nanosafety. However, the dynamics of intracellular release and exchange of the protein corona from nanomaterials remains unclear, and the biological footprints of the nanoparticle-protein corona inside cells are not well understood. This study investigates the evolution of the intracellular protein corona along the endocytotic pathway and reveals its impact on cell metabolism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Cell Biology
Yi-Ting Wang, Guang-Chao Chen
Summary: This study revealed the critical role of ATG9A ubiquitination in oxidative stress-induced autophagy, endocytic trafficking, and innate immunity. TRAF6 mediates ATG9A ubiquitination, promoting autophagy activation, while TNFAIP3/A20 acts as a negative regulator of oxidative stress-induced autophagy.
Article
Multidisciplinary Sciences
Mengshu Jia, Xiao Yue, Weixia Sun, Qianjun Zhou, Cheng Chang, Weihua Gong, Jian Feng, Xie Li, Ruonan Zhan, Kemin Mo, Lijuan Zhang, Yajie Qian, Yuying Sun, Aoxue Wang, Yejun Zou, Weicai Chen, Yan Li, Li Huang, Yi Yang, Yuzheng Zhao, Xiawei Cheng
Summary: In this study, it was found that lactate dehydrogenase A (LDHA) is activated upon UNC-51-like kinase 1 (ULK1) activation under nutrient deprivation, and promotes lactate production through Vps34 lactylation. These findings describe the interplay between autophagy and glycolysis.
Article
Cell Biology
Ting Zhu, Bo Liu, Di Wu, Gang Xu, Yang Fan
Summary: The study revealed that autophagy regulates erastin-induced ferroptosis through the FBXW7-VDAC3 axis, with rapamycin sensitizing ALL cells to erastin-induced ferroptosis. This provides potential therapeutic targets for acute lymphoblastic leukemia.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Sonia Ravanelli, Qiaochu Li, Andrea Annibal, Aleksandra Trifunovic, Adam Antebi, Thorsten Hoppe
Summary: Using genetics and multi-omics analyses, researchers have found a link between branched-chain amino acid metabolism and the regulation of the ubiquitin-proteasome system. This sheds light on the role of branched-chain amino acids in the aging process and opens up possibilities for future therapeutic interventions.
Article
Cell Biology
Jun Jun Jia, Xiao Yan Liao, Yi Yun Liang, Rui Ling Chen, Feng Guang Gao
Summary: K48 and K27-linked ubiquitination play vital roles in cross-presentation and BMPC-based adaptive immunity by affecting BMPC cross-presentation and cytolytic capacity in BMPC-activated T cells.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ya-Yun Chen, Xiang-Hong Ran, Run-Ze Ni, Dan Mu
Summary: TRIM28 is identified as a negative regulator of the RLR signaling pathway by targeting MAVS for proteasome-mediated degradation, which inhibits the production of type I interferons and proinflammatory cytokines induced by MAVS.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Rongxin Li, Dan Zhang, Yueqing Han, Ke Chen, Weiran Guo, Yijun Chen, Shuzhen Wang
Summary: In this study, the researchers found that the expression of EphB1 is significantly increased in activated HSCs, accompanied by remarkable neddylation. This neddylation enhances the kinase activity of EphB1, promoting HSC proliferation, migration, and activation, and thus contributing to the development of liver fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Jing Su, Tiantian Jiao, Xi Liu, Lingcheng Zhu, Baiquan Ma, Fengwang Ma, Mingjun Li
Summary: Fructokinase activates fructose through phosphorylation, but the overexpression of the apple FRK gene MdFRK2 leads to higher fructose levels in transgenic apple fruits. Further analysis reveals an MdCacyBP-MdFRK2 regulatory module that controls fructose homeostasis in different organs by ubiquitination and degradation of MdFRK2. This study provides useful insights into improving apple flavor and understanding plant fructose regulation.
Article
Geriatrics & Gerontology
Ana Maria Cuervo, Derek M. Huffman, Jan Vijg, Sofiya Milman, Rajat Singh, Nir Barzilai
Summary: The Einstein-Nathan Shock Center aims to make scientific discoveries in geroscience, translate them towards drug discovery, and confirm their relevance to humans. Through cutting-edge research programs and unique support cores, the center integrates key hallmarks of aging and facilitates translational biological research programs. The collaborative nature of the supporting research cores forms the foundation of research success at the E-NSC, allowing for expansion in translational research and new drug design services targeting the hallmarks of aging.
Article
Telecommunications
Shujuan Wang, Qian Zhang, Guangchao Chen
Summary: The article discusses the importance of Internet of Vehicles (IoVs) in enhancing traffic safety and reducing losses from traffic accidents. By utilizing a cooperative video alert dissemination mechanism between vehicles, it effectively decreases accident video transmission delays and increases user satisfaction.
VEHICULAR COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Fei-Yang Tzou, Jung-Kun Wen, Jui-Yu Yeh, Shu-Yi Huang, Guang-Chao Chen, Chih-Chiang Chan
Summary: Autophagy plays a crucial role in maintaining cellular homeostasis by degrading and recycling cytosolic components, and its disruption has been linked to neurodegenerative diseases. The fruit fly Drosophila has been used as a model system to study the role of autophagy in neurodegenerative diseases, providing valuable mechanistic evidence.
Article
Optics
Dongxia Li, Lizhen Zeng, Yuanli Wang, Hong-Wen Tang, Wen Xing Lee, Zhencheng Chen, Longhui Zhang, Yingchang Zou, Duan Xie, Fangrong Hu
Summary: We propose a method for diagnosing cirrhosis and hepatocellular carcinoma (HCC) using a terahertz metamaterial biosensor. The biosensor can measure the concentration of alpha-fetoprotein (AFP) in serum and shows a positive correlation with AFP levels in HCC patients.
Article
Environmental Sciences
Wieneke Bil, Veronika Ehrlich, Guangchao Chen, Rob Vandebriel, Marco Zeilmaker, Mirjam Luijten, Maria Uhl, Philip Marx-Stoelting, Thorhallur Ingi Halldorsson, Bas Bokkers
Summary: Relative potency factors (RPFs) for immune suppressive effects of PFAS were successfully derived using data from rodents and humans.
ENVIRONMENT INTERNATIONAL
(2023)
Review
Biochemistry & Molecular Biology
Xujun Han, Kah Yong Goh, Wen Xing Lee, Sze Mun Choy, Hong-Wen Tang
Summary: The mechanistic target of rapamycin (mTOR) complex 1, mTORC1, plays critical roles in regulating cell growth, proliferation, and lifespan by integrating nutrient and growth factor signals. It has been reported as a central regulator of autophagy, modulating almost all aspects of the autophagic process. mTORC1 and autophagy are important for skeletal muscle function and are implicated in various muscle diseases. Targeting mTORC1 or autophagy pathways with inhibitors has shown potential in the treatment of muscle diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Yue Liu, Xiaobing Chen, Jianchen Zhao, Wenjie Jin, Kun Zhang, Jiao Qu, Ya-nan Zhang, Guangchao Chen, Willie J. G. M. Peijnenburg
Summary: Organic compounds can generate hydroxyl radicals (OH) through excited triplet states, and investigating their generation mechanism and quantum yield is crucial for understanding indirect photochemical processes in the environment. In this study, the OH quantum yields of 20 organic compounds were determined experimentally and a quantitative structure-activity relationship (QSAR) model was developed to predict the yields for organic pollutants. The results indicate that electron distribution and electronegativity of organic compounds are the main factors determining OH generation.
ENVIRONMENTAL SCIENCE-PROCESSES & IMPACTS
(2023)
Article
Engineering, Electrical & Electronic
Shujuan Wang, Guangchao Chen, Yanxiang Jiang, Xiaohu You
Summary: This paper proposes a Cluster-based Vehicle-to-Vehicle approach for Mixed Data Dissemination in urban scenario of Internet of Vehicles. The approach utilizes buses as cluster heads and analyzes multiple characteristics to achieve efficient data dissemination. It also introduces a new priority calculation method to meet the QoS requirements of emergency and service messages.
IEEE TRANSACTIONS ON VEHICULAR TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Meng-Ru Ho, Yi-Ming Wu, Yen-Chen Lu, Tzu-Ping Ko, Kuen-Phon Wu
Summary: In this study, a cryo-electron microscopy (cryo-EM) structure of a 723-amino acid protein called malate synthase G (MSG) from Escherichia coli was determined at a resolution of 2.9 A. The cryo-EM structure of this 82-kDa protein was found to be similar to structures resolved by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, with no distinguishable differences. The study also revealed consistent conformational flexibilities among different experimental approaches, particularly in the alpha/beta domain. Additionally, differences in sidechain rotations of certain residues involved in hosting the cofactor acetyl-CoA and substrate were observed between the cryo-EM apo-form and complex crystal structures. These findings demonstrate that cryo-EM can be used to determine the structures and conformational heterogeneity of sub-100 kDa biomolecules with a quality comparable to X-ray crystallography and NMR spectroscopy.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Chiwei Xu, Jun Xu, Hong-Wen Tang, Maria Ericsson, Jui-Hsia Weng, Jonathan DiRusso, Yanhui Hu, Wenzhe Ma, John M. Asara, Norbert Perrimon
Summary: Little is known about intracellular P-i metabolism and signaling in animal tissues. This study found that P-i starvation triggers the downregulation of the P-i transporter PXo and causes midgut hyperproliferation in Drosophila melanogaster. It was also discovered that PXo specifically marks non-canonical organelles called PXo bodies, which function as intracellular P-i reserves and undergo degradation during P-i starvation. Additionally, the study identified Cka as the mediator of PXo knockdown- or P-i starvation-induced hyperproliferation.
Article
Multidisciplinary Sciences
Yu-Hsuan Chen, Han-Hsiun Chen, Won-Jing Wang, Hsin-Yi Chen, Wei-Syun Huang, Chien-Han Kao, Sin-Rong Lee, Nai Yang Yeat, Ruei-Liang Yan, Shu-Jou Chan, Kuen-Phon Wu, Ruey-Hwa Chen
Summary: Activation of tumor-intrinsic innate immunity is crucial for improving immunotherapy. The deubiquitinating enzyme TRABID is found to play a suppressive role in anti-tumor immunity by regulating mitotic cell division and activating the cGAS/STING pathway. TRABID inhibition induces micronuclei and protects cGAS from autophagy, thus promoting anti-tumor immune responses.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Hong-Wen Tang, Kerstin Spirohn, Yanhui Hu, Tong Hao, Istvan A. Kovacs, Yue Gao, Richard Binari, Donghui Yang-Zhou, Kenneth H. Wan, Joel S. Bader, Dawit Balcha, Wenting Bian, Benjamin W. Booth, Atina G. Cote, Steffi de Rouck, Alice Desbuleux, Kah Yong Goh, Dae-Kyum Kim, Jennifer J. Knapp, Wen Xing Lee, Irma Lemmens, Cathleen Li, Mian Li, Roujia Li, Hyobin Julianne Lim, Yifang Liu, Katja Luck, Dylan Markey, Carl Pollis, Sudharshan Rangarajan, Jonathan Rodiger, Sadie Schlabach, Yun Shen, Dayag Sheykhkarimli, Bridget TeeKing, Frederick P. Roth, Jan Tavernier, Michael A. Calderwood, David E. Hill, Susan E. Celniker, Marc Vidal, Norbert Perrimon, Stephanie E. Mohr
Summary: This study uses advanced methods to identify protein-protein interactions in Drosophila, generating widely useful physical and data resources for the identification of new components in pathways, complexes, and processes. The generation of reference maps of interactome networks provides a protein-centric approach to discover new components in existing pathways, complexes, and processes, which is helpful for genetic studies. The results include the FlyBi dataset and the DroRI reference interaction network, which provide a foundation for building new hypotheses about protein networks and function.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Ta Hung, Yun-Jung Hsieh, Wei-Lin Lu, Amy Keating, Kuen-Phon Wu, Chia-en A. Chang
Summary: This study uses computational modeling to reveal the essential residue interaction network and dihedral angle correlations in protein-protein recognition. By mutating residues with highly correlated dynamic motion within the interaction network, the study shows an effective approach to optimize protein-protein interactions and create tight and selective protein binders.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuan-Chao Lou, Hsuan-Yu Huang, Hsin-Hong Yeh, Wei-Hung Chiang, Chinpan Chen, Kuen-Phon Wu
Summary: This study reports the structure of a bacterial PmrA-dependent transcription activation complex, which reveals that RNAPH interacts with the C-terminal DNA-binding domain of PmrA via electrostatic interactions and reorients the DBD, resulting in a dynamic TAC conformation. In vivo assays show that substitution of the DNA-recognition residue eliminates its transcriptional activity, while variants with altered RNAPH-interacting residues result in enhanced transcriptional activity. These findings suggest the importance of both PmrA recognition-induced DNA distortion and promoter escape in its transcriptional activation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Shaifali Singh, Nai Yang Yeat, Ya-Ting Wang, Shu-Yu Lin, I-Ying Kuo, Kuen-Phon Wu, Won-Jing Wang, Wen-Ching Wang, Wu-Chou Su, Yi-Ching Wang, Ruey-Hwa Chen
Summary: WDR4/PTPN23 axis plays a central role in the trafficking of EGFR and c-MET in non-small cell lung cancer (NSCLC). WDR4-mediated PTPN23 ubiquitination inhibits lysosome trafficking and degradation, sustaining EGFR and c-MET signaling and promoting NSCLC proliferation, migration, and metastasis. Clinical studies show that low expression of PTPN23 is associated with high expression of WDR4 and poor prognosis in lung cancer. Targeting WDR4-mediated PTPN23 ubiquitination may be a potential therapeutic strategy for EGFR TKI-resistant NSCLC.
CELL DEATH & DISEASE
(2023)
Article
Biochemical Research Methods
Hsi-Wen Kao, Wei-Lin Lu, Meng-Ru Ho, Yu-Fong Lin, Yun-Jung Hsieh, Tzu-Ping Ko, Shang-Te Danny Hsu, Kuen-Phon Wu
Summary: We used ProteinMPNN, a deep learning tool, to redesign ubiquitin (Ub) as a specific and functionally stimulating/enhancing binder of the Rsp5 E3 ligase. We generated 20 extensively mutated Ub variants (UbVs) named R1 to R20, which displayed well-folded structures and high thermal stabilities. These UbVs can form stable complexes with Rsp5, as predicted by AlphaFold2. Three of the UbVs showed low micromolar affinity to Rsp5, with R4 and R12 effectively enhancing Rsp5 activity six folds. AlphaFold2 predicts that R4 and R12 bind to Rsp5's exosite in the same manner as the Rsp5-Ub template, thereby allosterically activating Rsp5-Ub thioester formation. Thus, we present a virtual solution for rapidly and cost-effectively designing functional modulators of Ub-related enzymes.
ACS SYNTHETIC BIOLOGY
(2023)