Editorial Material
Cell Biology
Lidia Wrobel, Sandra M. Hill, David C. Rubinsztein
Summary: Maintaining a functional proteome by removing damaged or misfolded proteins is crucial for cell survival. In many neurodegenerative diseases, such as Huntington, Alzheimer's, and Parkinson's diseases, aggregate-prone proteins accumulate. The ubiquitin-proteasome system and autophagy are the main pathways for protein clearance, but their activity declines with disease or age. Recent research has shown that targeting VCP/p97 and using compounds like SMER28 can enhance autophagy flux and stimulate protein clearance through the ubiquitin-proteasome system. This dual action leads to a selective decrease in disease-causing proteins.
Article
Biochemistry & Molecular Biology
Robert F. Shearer, Dimitris Typas, Fabian Coscia, Sofie Schovsbo, Thomas Kruse, Andreas Mund, Niels Mailand
Summary: Ubiquitin conjugation to substrate proteins regulates cellular processes and the K27 linkage type is essential for human cell proliferation. K27-linked ubiquitylation predominantly occurs in the nucleus and its disruption impairs nuclear ubiquitylation dynamics and cell cycle progression. K27-linked ubiquitylation supports cell fitness by facilitating p97-dependent processing of ubiquitylated nuclear proteins.
Article
Multidisciplinary Sciences
Yuki Toyama, Lewis E. Kay
Summary: Developments in solution NMR spectroscopy have significantly impacted the ability to address biological questions, especially in studying molecular machines critical for cellular homeostasis. NMR plays a key role in elucidating the structural dynamics of important molecules, highlighting intersubunit allosteric communication in homo-oligomers. Through focused experimental studies on individual subunits and the preparation of asymmetric molecules, intersubunit allostery can be directly observed in high-molecular-weight protein systems, showcasing the unique contributions of solution NMR spectroscopy in studying complex biomolecules and emphasizing the synergy between NMR and other atomic resolution biophysical methods.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Trevor van Eeuwen, Yoonjung Shim, Hee Jong Kim, Tingting Zhao, Shrabani Basu, Benjamin A. Garcia, Craig D. Kaplan, Jung-Hyun Min, Kenji Murakami
Summary: The study presents a cryo-EM structure of an NER initiation complex, showing how the XPC-RAD23B-CETN2 complex and TFIIH complex work together to recognize and verify DNA lesions. This interaction allows for unwinding of DNA and delivery of damaged strands for subsequent scanning and verification.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Maria Koerner, Susanne R. Meyer, Gabriella Marincola, Maximilian J. Kern, Clemens Grimm, Christina Schuelein-Voelk, Utz Fischer, Kay Hofmann, Alexander Buchberger
Summary: The ATPase p97, a crucial regulator in various cellular processes, is linked to neuromuscular diseases and cancer. This study identifies the previously unknown FAM104 proteins as a family of p97 interactors. The two human members of the family, VCP nuclear cofactor family member 1 and 2 (VCF1/2), directly bind p97 and associate with p97 complexes in cells. They localize to the nucleus and promote the nuclear import of p97. Loss of VCF1/2 leads to reduced nuclear p97 levels, slow growth, and hypersensitivity to chemical inhibition of p97.
Review
Oncology
Johannes Tobias Thiel, Adrien Daigeler, Jonas Kolbenschlag, Katarzyna Rachunek, Sebastian Hoffmann
Summary: Soft tissue sarcomas (STSs) are rare malignant conditions that are difficult to treat. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong driver of sarcogenesis. This review discusses the role of CDK signaling in STS development and its implications for targeted treatment.
Review
Cell Biology
Aleksandra J. Pluta, Cecilia Studniarek, Shona Murphy, Chris J. Norbury
Summary: This article discusses the important roles of structurally related cyclin-dependent protein kinases (CDKs) in eukaryotic cell function, highlighting their roles in cell cycle regulation and transcriptional regulation, and the overlap between these processes.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Biochemistry & Molecular Biology
Kaiyuan Zhu, Yang Cai, Xiaotong Si, Zuodong Ye, Yuanzhu Gao, Chuang Liu, Rui Wang, Zhibin Ma, Huazhang Zhu, Liang Zhang, Shengjin Li, Hongmin Zhang, Jianbo Yue
Summary: By regulating the phosphorylation and dephosphorylation switch of VCP, the architecture of centrosome and spindle is controlled to ensure faithful chromosome segregation.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Yilun Sun, Eroica Soans, Margarita Mishina, Elena Petricci, Yves Pommier, Karin C. Nitiss, John L. Nitiss
Summary: This study investigated the covalent complexes between TOP2 protein and DNA using an optimized ICE assay. The results showed that the absence or inhibition of MRE11 resulted in elevated levels of TOP2 covalent complexes, while overexpression of MRE11 could remove TOP2 covalent complexes. In addition, inhibition of VCP/p97 led to increased levels of TOP2 covalent complexes and prevented the removal of TOP2 covalent complexes by MRE11 overexpression. These findings suggest the existence of multiple pathways for proteolytic processing of TOP2 prior to nucleolytic processing.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Pawel Lukasik, Irena Baranowska-Bosiacka, Katarzyna Kulczycka, Izabela Gutowska
Summary: Recent studies have shown that small molecule drugs targeting CDK inhibitors have become attractive options for treating cancer and neurodegenerative disorders. Most CDK inhibitors target the ATP binding pocket, but the similarity in structure among CDK kinases makes achieving selectivity challenging. Therefore, inhibitors binding outside the ATP binding site have attracted great interest for their potential applications in the biomedical field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Susan Kilgas, Kristijan Ramadan
Summary: Protein homeostasis deficiencies are the foundation of various cancers and neurodegenerative diseases. The UPS and autophagy systems, responsible for protein degradation in mammalian cells, are attractive targets for cancer therapy and neurodegenerative disease treatment. The p97 ATPase, also known as VCP, is a central part of UPS and regulates autophagy. Multiple p97 inhibitors, including CB-5083 and CB-5339, have shown effective anti-tumor activity in clinical trials, providing an alternative approach for targeting protein degradation in cancer therapy. This review provides an overview of the development of different p97 inhibitors as research tools and cancer therapies targeting UPS.
CELL CHEMICAL BIOLOGY
(2023)
Review
Oncology
Ajay Dhaka, Carla Falkson, Ruth M. O'Regan
Summary: The use of CDK4/6 inhibitors has improved outcomes for patients with metastatic HR-positive breast cancer, but trials evaluating their use in the adjuvant setting have shown mixed results, highlighting the need for further research on patient selection and predictive biomarkers.
Article
Oncology
Emanuel Raschi, Michele Fusaroli, Andrea Ardizzoni, Elisabetta Poluzzi, Fabrizio De Ponti
Summary: This post-marketing research studied the role of cyclin-dependent kinase 4/6 inhibitors in cancer-associated thrombosis, finding a potential class effect for venous thrombosis and distinctive arterial events for ribociclib. The study suggests proactive monitoring by oncologists for thromboembolic events with CDK4/6 inhibitors and supports pharmacovigilance for safe prescribing in oncology.
Article
Cell Biology
Souradeep Basu, James O. Patterson, Theresa U. Zeisner, Paul Nurse
Summary: The range of CDK activity and its impact on cell cycle progression has been unknown. A study in fission yeast revealed that sublethal CDK inhibition can lengthen the time cells spend in mitosis without causing misordering of mitotic events. The maximum attainable CDK activity forms a buffer that ensures mitotic completion when CDK activity is compromised.
JOURNAL OF CELL SCIENCE
(2022)
Article
Geriatrics & Gerontology
Ying Huang, Bin Wang, Faten Hassounah, S. Russ Price, Janet Klein, Tamer M. A. Mohamed, Yanhua Wang, Jeanie Park, Hui Cai, Xuemei Zhang, Xiaonan H. Wang
Summary: In this study, the researchers found that senescent muscle precursor cells (MPCs) may contribute to muscle wasting in CKD by producing inflammatory cytokines. The use of senolytics improved muscle wasting and muscle strength, and restored MPC function.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Immunology
Hui Wang, Xiangjie Lin, Yuan Luo, Shaoxing Sun, Xiaoli Tian, Yingming Sun, Shimin Zhang, Jing Chen, Junhong Zhang, Xuefeng Liu, Huan Liu, Yan Gong, Conghua Xie
Article
Genetics & Heredity
Anil K. Chauhan, Yingming Sun, Qianzheng Zhu, Altaf A. Wani
Summary: The article summarizes the roles of the ubiquitin-proteasome system (UPS) in regulating nucleotide excision repair (NER), including the ubiquitination and deubiquitination processes of DNA damage sensors during DNA repair, as well as the involvement of new regulators of NER.
Review
Materials Science, Biomaterials
Zhenjie Yin, Bingyong You, Yuanyuan Bai, Yu Zhao, Shangfan Liao, Yingming Sun, Yongyang Wu
Summary: Renal cell carcinoma (RCC) represents the majority of malignant kidney cancers, and there has been substantial progress in therapeutic options for RCC in the past decade. Targeted therapy and immunotherapy have revolutionized RCC treatment and improved outcomes; however, adverse effects and drug resistance remain significant challenges. Natural compounds have gained attention as alternative strategies due to their tolerability and cost-effectiveness. Numerous studies have investigated the anti-RCC activity of natural products and identified potential mechanisms. This article provides a review on the chemoprevention and therapeutic potential of natural compounds, as well as explores their underlying mechanisms.
Article
Cell Biology
Jia Luo, Yigui Jiang, Lianhui Wu, Dexiang Zhuo, Shengjun Zhang, Xiang Jiang, Yingming Sun, Yue Huang
Summary: The long non-coding RNA ABHD11-AS1 is overexpressed in colorectal cancer and promotes proliferation, migration, and invasion by activating the ITGA5/FAK/PI3K/Akt signaling pathway. Targeting the ITGA5/FAK/PI3K/Akt axis may hold promise for colorectal cancer therapy.
Article
Biochemistry & Molecular Biology
Yingming Sun, Xiaoge Sun, Chengcheng You, Shijing Ma, Yuan Luo, Shan Peng, Fang Tang, Xiaoli Tian, Feng Wang, Zhengrong Huang, Hongnv Yu, Yu Xiao, Xiaoyong Wang, Junhong Zhang, Yan Gong, Conghua Xie
Summary: MUC3A is highly expressed in non-small cell lung cancer (NSCLC) and associated with poor prognosis, advanced staging, and low differentiation. Knockdown of MUC3A suppresses tumor growth and DNA damage repair pathways, suggesting it may be a potential oncogene.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yuan Luo, Shijing Ma, Yingming Sun, Shan Peng, Zihang Zeng, Linzhi Han, Shuying Li, Wenjie Sun, Jieyu Xu, Xiaoli Tian, Feng Wang, Qiuji Wu, Yu Xiao, Junhong Zhang, Yan Gong, Conghua Xie
Summary: The transmembrane mucin MUC3A induces PD-L1 expression in NSCLC, promoting immune escape, while downregulation of MUC3A enhances the effects of TKIs in EGFR-mutant NSCLC. Knocking down MUC3A reduces PD-L1 expression by downregulating the activation of the PI3K/Akt and MAPK pathways. In vitro, the combination of MUC3A knockdown and TKIs in EGFR-mutant NSCLC cells has a synergistic effect on inhibiting proliferation and promoting apoptosis.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Yingming Sun, Zhe Wang, Sufang Qiu, Ruoyu Wang
Summary: HNSCC, the 9th most common malignant tumor worldwide, can be divided into HPV-related and HPV-unrelated subtypes based on etiology. HPV-positive HNSCC is more sensitive to treatment with better survival rates, requiring individualized therapy. EGFR amplification and PI3K/AKT/mTOR pathway aberrant activation are common in HPV-positive HNSCC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Medicine, General & Internal
Xiyuan He, Shangfan Liao, Dongming Lu, Fabiao Zhang, Yingming Sun, Yongyang Wu
Summary: The research findings suggest that miR-125b plays a role in promoting migration, invasion, and inhibiting apoptosis in renal cell carcinoma, and is negatively correlated with VDR.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Oncology
Shangfan Liao, Huaibin Huang, Fabiao Zhang, Dongming Lu, Shuchao Ye, Luoping Zheng, Yingming Sun, Yongyang Wu
Article
Oncology
Wenxin Chen, Chuan Wang, Fangmeng Fu, Binglin Yang, Changming Chen, Yingming Sun
CANCER MANAGEMENT AND RESEARCH
(2020)
Article
Medicine, General & Internal
Yingming Sun, Xiaochuan Chen, Yajuan Zhou, Sufang Qiu, Yongyang Wu, Min Xie, Guofang Zhu, Shanshan Liang, Heming Li, Dong Zhou, Zaishuang Ju, Fuguang Wang, Fang Han, Zhe Wang, Ruoyu Wang
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Shan Peng, Yingming Sun, Yuan Luo, Shijing Ma, Wenjie Sun, Guiliang Tang, Shuying Li, Nannan Zhang, Jiangbo Ren, Yu Xiao, Xuefeng Liu, Junhong Zhang, Yan Gong, Conghua Xie
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Jieyu Xu, Yuan Luo, Cheng Yuan, Linzhi Han, Qiuji Wu, Liexi Xu, Yuke Gao, Yingming Sun, Shijing Ma, Guiliang Tang, Shuying Li, Wenjie Sun, Yan Gong, Conghua Xie
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Shijing Ma, Hongtao Miao, Yuan Luo, Yingming Sun, Xiaoli Tian, Feng Wang, Chengcheng You, Shan Peng, Guiliang Tang, Cui Yang, Wenjie Sun, Shuying Li, Yanling Mao, Jieyu Xu, Yu Xiao, Yan Gong, Hong Quan, Conghua Xie
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2019)