Review
Cell Biology
Yosup Kim, Eun-Kyung Kim, Yoona Chey, Min-Jeong Song, Ho Hee Jang
Summary: The proteasome is a multi-catalytic protease complex that regulates protein quality control. It selectively degrades cellular proteins through ubiquitination and plays a critical role in maintaining protein homeostasis. This article summarizes the proteasome's structure, regulatory mechanisms, proteins that control its activity, and its involvement in various diseases, chemoresistant cells, and cancer stem cells. Potential therapeutic modalities that target the ubiquitin-proteasome system are also discussed.
Review
Pharmacology & Pharmacy
Si-Min Qi, Jinyun Dong, Zhi-Yuan Xu, Xiang-Dong Cheng, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: PROTAC technology is an effective method for degrading target proteins through the ubiquitin-proteasome system, with promising applications in cancer treatment. The first oral PROTACs have shown encouraging results in clinical trials, sparking greater enthusiasm for PROTAC research.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Xinyi Li, Wenchen Pu, Qingquan Zheng, Min Ai, Song Chen, Yong Peng
Summary: PROTAC is an engineered technique for targeted protein degradation, which recruits target protein and E3 ubiquitin ligase to trigger the degradation of target protein. It has great potential in cancer therapy and offers advantages over traditional anti-cancer therapies.
Review
Cell Biology
Ming He, Wenxing Lv, Yu Rao
Summary: PROTAC is a new technology for inducing protein degradation using small molecules, which shows advantages in overcoming tumor resistance, affecting non-enzymatic functions of target proteins, degrading undruggable targets, and providing rapid and reversible chemical knockout tools. However, it also faces challenges and issues as a rapidly developing new chemical biology technology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Chemistry, Medicinal
Zonghui Ma, Yu Ji, Yifan Yu, Dailin Liang
Summary: PROTACs are a promising therapeutic strategy that catalytically induce target proteins degradation and potentially overcome drug resistance. SNIPERs, based on IAPs, can successfully degrade disease-associated target proteins, providing a new avenue for treating challenging diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Andrew B. Benowitz, Katherine L. Jones, John D. Harling
Summary: PROTACs are a novel class of heterobifunctional molecules that can modulate target biology uniquely compared to inhibitors, with potential to develop new medicines for treating multiple diseases. Delivering on the huge potential of PROTACs will require the development of differentiated PROTAC medicines from traditional inhibitors, which will pose both opportunities and challenges in securing robust intellectual property.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2021)
Article
Multidisciplinary Sciences
Afu Fu, Victoria Cohen-Kaplan, Noa Avni, Ido Livneh, Aaron Ciechanover
Summary: The degradation of proteins through the ubiquitin-proteasome system is a complex multistep process that relies on the coordinated activity of various enzymes. Nuclear condensates containing essential components like p62 play a crucial role in protein quality control and degradation, especially under stress conditions. These assemblies, generated through liquid-liquid phase separation, efficiently facilitate proteolysis of nuclear proteins and unassembled proteasome subunits, indicating their involvement in cellular protein quality control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Nobumichi Ohoka, Masanori Suzuki, Takuya Uchida, Genichiro Tsuji, Yoshinori Tsukumo, Masayuki Yoshida, Takao Inoue, Yosuke Demizu, Hitoshi Ohki, Mikihiko Naito
Summary: In this study, novel FLT3 degraders were developed by introducing an FDA-approved FLT3 inhibitor, gilteritinib, into targeted protein degradation technology. The most active compound, CRBN(FLT3)-8, potently degraded FLT3-ITD via the ubiquitin-proteasome system and effectively inhibited the proliferation of AML cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Medicinal
Fabian Fischer, Leandro A. Alves Avelar, Laoise Murray, Thomas Kurz
Summary: PROTACs are a powerful tool for degrading intracellular proteins by hijacking the UPS system, with potential for targeted HDAC degradation. This review discusses the key factors in the development of HDAC-PROTACs, including HDACi, linker, and E3 ligase ligand, and their impact on efficacy and selectivity.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Moyang Lv, Weichao Hu, Shengwei Zhang, Lijiao He, Changjiang Hu
Summary: Proteolysis-targeting chimeras (PROTACs) are a promising class of drugs that can effectively target undruggable proteins and have potential applications in cancer therapy. This review provides an overview of PROTAC technology and highlights recent clinical trials, as well as novel findings and strategies to enhance PROTAC antitumor activity.
Review
Biology
Soonsil Hyun, Dongyun Shin
Summary: Neurodegenerative diseases are characterized by dysfunction of cognition and mobility, often caused by aggregates of misfolded proteins. Recently, targeted protein degradation using small molecules has emerged as a promising new therapeutic approach for these challenging diseases. Various technologies, such as molecular glues, have shown success in degrading disease-related proteins and may hold potential for the treatment of neurodegenerative diseases caused by protein aggregation.
Article
Chemistry, Multidisciplinary
Hanqiao Xu, Nobumichi Ohoka, Hidetomo Yokoo, Kanako Nemoto, Takashi Ohtsuki, Hiroshi Matsufuji, Mikihiko Naito, Takao Inoue, Genichiro Tsuji, Yosuke Demizu
Summary: LXR degraders have been developed as a promising therapeutic approach for LXR-related diseases by effectively degrading LXR proteins, potentially serving as novel treatments for hypercholesterolemia and diabetes.
FRONTIERS IN CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Xiang Chen, Zaw Min Htet, Erika Lopez-Alfonzo, Andreas Martin, Kylie J. Walters
Summary: The 26S proteasome is responsible for regulated proteolysis in eukaryotic cells, with substrates targeted to it through post-translational modification with ubiquitin. Deubiquitinating enzymes (DUBs) play a crucial role in catalyzing ubiquitin chain hydrolysis, coupling deubiquitination to substrate unfolding and degradation. This intricate machinery of proteasomes and ubiquitin-modified substrates remains an active area of investigation, with potential for therapeutic targeting.
Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Review
Biochemistry & Molecular Biology
Na Yang, Bo Kong, Zhaohong Zhu, Fei Huang, Liliang Zhang, Tao Lu, Yadong Chen, Yanmin Zhang, Yulei Jiang
Summary: Targeted protein degradation (TPD) technology, such as PROTACs, has become widespread in the past 20 years and greatly accelerates the development of disease treatment. Unlike small inhibitors, targeted protein degraders can target undruggable targets and overcome drug resistance through ubiquitin-proteasome pathway (UPP) and lysosome pathway. This review discusses different degradation technologies and provides a basis for future research.
MOLECULAR DIVERSITY
(2023)
Article
Physics, Multidisciplinary
Fei Li, Yuqin Yao
Summary: Based on the high-order restricted flows of the extended fifth-order KdV equation, the efKdV equation with self-consistent sources (efKdVESCS) is presented and its Lax pair is constructed. Two types of Nth Darboux transformations for the efKdVESCS are constructed. Various types of solutions including one-soliton, two-soliton, and rational solution are explicitly obtained using Darboux transformations.
THEORETICAL AND MATHEMATICAL PHYSICS
(2022)
Article
Engineering, Mechanical
Yehui Huang, Jingjing Di, Yuqin Yao
Summary: The defocusing Hirota equation with nonzero boundary condition is studied using the partial derivative-dressing method. A partial derivative-problem with non-canonical normalization conditions is introduced. The Lax pair of the defocusing Hirota equation with nonzero boundary condition is derived using an asymptotic expansion method. N-soliton solutions are constructed under a selected special spectral transformation matrix, and the dynamic behavior of soliton solutions is analyzed.
NONLINEAR DYNAMICS
(2023)
Article
Chemistry, Medicinal
Xingping Su, Zui Tan, Guan Wang, Zhihao Liu, Cailing Gan, Lin Yue, Hongyao Liu, Yuting Xie, Yuqin Yao, Tinghong Ye
Summary: This study suggests that compounds 44 and 52 may serve as potential lead compounds for the treatment of idiopathic pulmonary fibrosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Rheumatology
Li Zhang, Wenqiang Zhang, Chenghan Xiao, Xueyao Wu, Huijie Cui, Peijing Yan, Chao Yang, Mingshuang Tang, Yutong Wang, Lin Chen, Yunjie Liu, Yanqiu Zou, Lars Alfredsson, Lars Klareskog, Yanfang Yang, Yuqin Yao, Jiayuan Li, Zhenmi Liu, Chunxia Yang, Xia Jiang, Ben Zhang
Summary: A comprehensive genome-wide cross-trait analysis revealed the genetic overlaps, pleiotropic loci, and causal relationships between obesity, serum urate, and gout.
Article
Toxicology
Shanshan Zhao, Qixue Bao, Guochen Ma, Yuqin Yao, Linshen Xie, Jingyuan Xiong
Summary: In this study, we investigated the effects of benzo[b]fluoranthene (B[b]F), a main component of polycyclic aromatic hydrocarbons (PAHs), on blood-brain barrier (BBB) in an in vitro model. The results showed that B[b]F inhibited cell proliferation, induced apoptosis, increased levels of reactive oxygen species (ROS), and disrupted mitochondrial membrane potential (MMP) in mouse brain microvascular endothelial cells. Moreover, B[b]F treatment reduced the expression of BBB marker proteins Occludin and Claudin-5, suggesting that it may damage the BBB.
TOXICOLOGY IN VITRO
(2023)
Article
Nutrition & Dietetics
Liqun Wang, Manyu Zhao, Rui Qian, Mengzhu Wang, Qixue Bao, Xuxi Chen, Wen Du, Ling Zhang, Tinghong Ye, Yongmei Xie, Ben Zhang, Lijun Peng, Yuqin Yao
Summary: In this study, it was found that NMN alleviates silica-induced oxidative stress and lung injury by reducing reactive oxygen species levels, increasing glutathione levels, inhibiting the recruitment of inflammatory cells and inflammatory infiltration, as well as regulating the expression and nuclear translocation of antioxidant genes through the interaction with nuclear factor-erythroid 2 related factor 2 (Nrf2).
Article
Biochemistry & Molecular Biology
Ying Lu, Mengzhu Wang, Manyu Zhao, Qianru Zhang, Rui Qian, Zan Hu, Qi Ke, Lin Yu, Liqun Wang, Qinhuai Lai, Zhenmi Liu, Xia Jiang, Ben Zhang, Jinliang Yang, Yuqin Yao
Summary: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by steatosis, inflammation, and fibrosis. This study found that the expression of Filamin A (FLNA) was increased in liver tissues of NASH patients and mice with NAFLD/NASH. Knocking down FLNA reduced the inflammatory response in macrophages and decreased fibrotic cytokines in hepatic stellate cells, suggesting FLNA's role in the pathogenesis of NASH.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Computer Science, Information Systems
Yuqin Yao, Hua Meng, Yang Gao, Zhiguo Long, Tianrui Li
Summary: Dimensionality reduction is a significant data preprocessing technique. This article analyzes the drawbacks of the traditional linear unsupervised dimensionality reduction method LPP and proposes an improved model to resolve them. Furthermore, the article enhances LPP to maintain topological connectivity of data. Experimental results demonstrate that the new model outperforms the original LPP model and other classic linear or non-linear dimensionality reduction methods.
INFORMATION SCIENCES
(2023)
Article
Toxicology
Qixue Bao, Shanshan Zhao, Yongqi Liu, Yuqin Yao, Jia You, Jingyuan Xiong
Summary: This study investigated the cytotoxicity of BbF on human lung epithelial cells and bronchial epithelial cells, and found that BbF inhibited cell growth and induced apoptosis through the ROS-mediated mitochondria disruption pathway.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Article
Engineering, Mechanical
Yuqin Yao, Hui Zhou, Fei Li
Summary: Based on higher-order restricted flows, the first type of integrable deformed fourth-order matrix NLS equations, called FMNLSSCS, is derived. By using the partial derivative-dressing method, the second type of integrable deformed fourth-order matrix NLS equations, called FMNLS-MB, is presented. The equivalence between FMNLSSCS and FMNLS-MB is successfully proved and N-soliton solutions are obtained explicitly using the Cauchy matrix method.
NONLINEAR DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Liqun Wang, Yali Li, Rui Xia, Xinyue Zheng, Xingjie Li, Shouxun Wu, Qianyu Zhang, Sha Li, Yuanle Deng, Yuqin Yao, Tinghong Ye, Wenya Yin
Summary: This study discovered that Rosa sterilis juice has anti-pulmonary fibrosis effects, and the high levels of polyphenols, flavonoids, and vitamin C may be the basic anti-fibrosis substances.
Proceedings Paper
Computer Science, Artificial Intelligence
Yuqin Yao, Yang Gao, Zhiguo Long, Hua Meng, Michael Sioutis
Summary: This paper proposes a hierarchical way of similarity matrix construction to describe relations between data points at different levels, which has better adaptability for complex data with multiple connected components.
2022 IEEE THE 5TH INTERNATIONAL CONFERENCE ON BIG DATA AND ARTIFICIAL INTELLIGENCE (BDAI 2022)
(2022)
Review
Biochemistry & Molecular Biology
Manyu Zhao, Liqun Wang, Mengzhu Wang, Shijie Zhou, Ying Lu, Huijie Cui, Alexandra C. Racanelli, Ling Zhang, Tinghong Ye, Bisen Ding, Ben Zhang, Jinliang Yang, Yuqin Yao
Summary: Fibrosis is a common pathological process in which excessive extracellular matrix deposition occurs due to dysregulated wound and connective tissue repair response. This review provides an overview of the etiology and epidemiology of several fibrosis diseases, as well as discussing the abnormal cells and their interactions, signaling pathways, and therapeutic targets involved in fibrosis. It also highlights the potential of anti-fibrotic drugs in targeting these mechanisms. This review serves as a valuable reference for further research, drug development, and clinical trials in the field of fibrosis.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Mathematics, Applied
Siqi Zhou, Jiapeng Liu, Siran Chen, Yuqin Yao
Summary: Non-local problems and integrable non-local nonlinear Schrödinger equation have attracted significant research attention. In this paper, we derive the PT-symmetry second derivative nonlinear Schrödinger equation and present the nth-Darboux transformation of the equation. We also provide explicit expressions for various soliton solutions of the PT-DNLSII equation.
JOURNAL OF NONLINEAR MATHEMATICAL PHYSICS
(2022)
Article
Respiratory System
Cailing Gan, Qianyu Zhang, Hongyao Liu, Guan Wang, Liqun Wang, Yali Li, Zui Tan, Wenya Yin, Yuqin Yao, Yongmei Xie, Liang Ouyang, Luoting Yu, Tinghong Ye
Summary: Nifuroxazide (NIF) shows potential as a treatment option for idiopathic pulmonary fibrosis (IPF) by inhibiting and reversing the development of pulmonary fibrosis. The findings of this study are important for exploring pharmaceutical treatments for pulmonary fibrosis.
RESPIRATORY RESEARCH
(2022)
