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
Neurosciences
Siwei Chu, Xinyi Xie, Carla Payan, Ursula Stochaj
Summary: The AAA(+) ATPase valosin containing protein (VCP) is crucial for maintaining the stability of cells and organs, especially in the nervous system. VCP collaborates with various cofactors to ensure proteostasis and is linked to human health through numerous mutations. Dysfunctional VCP is associated with neurodegeneration and other diseases, as it is responsible for dismantling protein aggregates and removing dysfunctional organelles. Further research is needed to uncover the molecular mechanisms connecting VCP mutations to specific brain pathologies and explore its potential as a drug target for neurodegeneration.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemical Research Methods
L. Ramya, S. Helina Hilda
Summary: Multiple Sclerosis (MS) is a demyelinating disease that disrupts the flow of brain signals. This article focuses on the role of intrinsically disordered proteins (IDP) in MS, and finds that the IDRs of these proteins play a significant role in maintaining myelin integrity.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2023)
Article
Clinical Neurology
Yoon Seob Kim, Don Gueu Park, Min Seung Kim, Jung Han Yoon
Summary: This case report presents a 53-year-old patient with Parkinson's disease and a VCP mutation who developed motor complications. The patient underwent subthalamic nucleus deep brain stimulation at 56 years old, but myopathy emerged 1.5 years after the surgery. The variability of VCP phenotype should be taken into consideration when evaluating the long-term outcomes of deep brain stimulation.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Microbiology
Rui-cong Sun, Jia-huan Hu, Xiao-han Li, Chun-chun Liu, Ya-yun Liu, Jing Chen, Yi-chen Yang, Bin Zhou
Summary: This study demonstrates for the first time that VCP is essential for the infection of CSFV and plays a key role in its intracellular transport. The findings provide an alternative approach for the discovery of novel anti-flaviviridae drugs.
VETERINARY MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram
Summary: This review discusses different aspects of disordered proteins and protein regions, as well as the experimental and computational methods used to characterize them. Additionally, the role of disordered proteins in diseases and their potential as drug targets are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
H. Jane Dyson
Summary: Viruses infect all kingdoms of life and employ disordered proteins to accomplish various functions. Disordered proteins have been discovered in almost all viruses studied, regardless of the viral genome composition or the viral capsid configuration. This review presents a collection of stories illustrating the diverse functions of disordered proteins in viruses, providing a survey of the field's expansion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sandra M. Hill, Lidia Wrobel, Avraham Ashkenazi, Marian Fernandez-Estevez, Keith Tan, Roland W. Burli, David C. Rubinsztein
Summary: VCP is a key regulator in the early initiation of autophagy, playing a role in stabilizing Beclin-1 levels and regulating the activity of the PI3K complex to increase the production of the signaling lipid PI(3)P. Decreased VCP levels or inhibition of its ATPase activity impairs autophagosome formation by limiting downstream recruitment of essential autophagy factors.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Dan Wang, Shaowen Wu, Dongdong Wang, Xingyu Song, Maohua Yang, Wolun Zhang, Shaohui Huang, Jingwei Weng, Zhijun Liu, Wenning Wang
Summary: This study investigates the interaction mechanism between protein 4.1G-CTD and NuMA using experimental and computational methods. The results demonstrate the importance of the compact disordered state of 4.1G-CTD for its binding to NuMA. This work sheds light on the molecular recognition mechanism of intrinsically disordered proteins/regions (IDPs/IDRs) and expands the conventional structure-function paradigm in protein biochemistry.
Review
Chemistry, Multidisciplinary
Matti Mar, Kateryna Nitsenko, Petur O. Heidarsson
Summary: Eukaryotic transcription factors play a crucial role in integrating molecular feedback and regulating gene expression. They consist of structured DNA-binding domains and long intrinsically disordered regions (IDRs). The dynamic multifunctionality of IDRs is essential for their functions in genome regulation. This review analyzes the chemical features of TF IDRs and their involvement in protein interactions, DNA binding, chromatin opening, and phase separation. Suggestions are given for future research to integrate experiments and simulations in understanding TF functions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Cell Biology
Abubakar Wani, Jiang Zhu, Jason D. Ulrich, Abdallah Eteleeb, Andrew D. Sauerbeck, Sydney J. Reitz, Khalid Arhzaouy, Chiseko Ikenaga, Carla M. Yuede, Sara K. Pittman, Feng Wang, Shan Li, Bruno A. Benitez, Carlos Cruchaga, Terrance T. Kummer, Oscar Harari, Tsui-Fen Chou, Rolf Schroder, Christoph S. Clemen, Conrad C. Weihl
Summary: Inactivating VCP and expressing disease-associated mutations in a mouse model revealed that loss of VCP-dependent functions is a mediator of FTLD-TDP, with unexpected biochemical similarity to progranulin deficiency.
Article
Biology
Rui Wu, Zhijie Wei, Li Zhang
Summary: Mutations in VCP are linked to various diseases, with R155C mutation considered the most deleterious. Different domains in the protein structure of the ATPase play distinct functional roles. Molecular analysis techniques provide insights into the effects of mutations on protein dynamics and ATP/ADP transition.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Vladimir D. Manyilov, Nikolay S. Ilyinsky, Semen V. Nesterov, Baraa M. G. A. Saqr, Guy W. Dayhoff, Egor V. Zinovev, Simon S. Matrenok, Alexander V. Fonin, Irina M. Kuznetsova, Konstantin K. Turoverov, Valentin Ivanovich, Vladimir N. Uversky
Summary: This article examines the impact of intrinsically disordered proteins and regions on aging-related processes. The findings indicate that these disordered components play significant roles in aging, particularly in genome regulation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Genetics & Heredity
Rod Carlo Agram Columbres, Yue Chin, Sanjana Pratti, Colin Quinn, Luis F. Gonzalez-Cuyar, Michael Weiss, Fabiola Quintero-Rivera, Virginia Kimonis
Summary: This study reports the clinical and genetic analysis findings in five patients with VCP gene mutations, including novel variants associated with MSP1 manifestations. The study highlights the heterogeneity in clinical symptoms and emphasizes the need for increased awareness and early consideration of MSP1 in the differential diagnosis of myopathies and/or PDB, dementia, or ALS to improve diagnosis and management.
Article
Physiology
Yusuke Hata, Ryosuke Date, Daisuke Fujimoto, Hanako Ohashi Ikeda, Shuro Umemoto, Tomoko Kanki, Yoshihiko Nishiguchi, Teruhiko Mizumoto, Manabu Hayata, Yutaka Kakizoe, Yuichiro Izumi, Akira Kakizuka, Masashi Mukoyama, Takashige Kuwabara
Summary: The novel findings of this study are as follows: 1) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiawen Wu, Dungeng Peng, Yang Zhang, Zhenwei Lu, Markus Voehler, Charles R. Sanders, Jun Li
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2015)
Article
Biophysics
Ji-Hun Kim, Jonathan P. Schlebach, Zhenwei Lu, Dungeng Peng, Kaitlyn C. Reasoner, Charles R. Sanders
BIOPHYSICAL JOURNAL
(2016)
Article
Biochemistry & Molecular Biology
Scott E. Collier, Markus Voehler, Dungeng Peng, Ryoma Ohi, Kathleen L. Gould, Nicholas J. Reiter, Melanie D. Ohi
Article
Biochemistry & Molecular Biology
Dungeng Peng, Ji-Hun Kim, Brett M. Kroncke, Cheryl L. Law, Yan Xia, Kristin D. Droege, Wade D. Van Horn, Carlos G. Vanoye, Charles R. Sanders
Meeting Abstract
Biophysics
Scott E. Collier, Dungeng Peng, Markus Voehler, Nicholas Reiter, Melanie Ohi
BIOPHYSICAL JOURNAL
(2014)
Meeting Abstract
Biophysics
Keenan C. Taylor, Po Wei Kang, Panpan Hou, Nien-Du Yang, Georg Kuenze, Jingyi Shi, Jarrod A. Smith, Kelli McFarland White, Hui Huang, Dungeng Peng, Alfred L. George, Jens Meiler, Robert L. McFeeters, Jianmin Cui, Charles R. Sanders
BIOPHYSICAL JOURNAL
(2019)
Article
Multidisciplinary Sciences
Nicholas G. Campbell, Aparna Shekar, Jenny I. Aguilar, Dungeng Peng, Vikas Navratna, Dongxue Yang, Alexander N. Morley, Amanda M. Duran, Greta Galli, Brian O'Grady, Ramnarayan Ramachandran, James S. Sutcliffe, Harald H. Sitte, Kevin Erreger, Jens Meiler, Thomas Stockner, Leon M. Bellan, Heinrich J. G. Matthies, Eric Gouaux, Hassane S. Mchaourab, Aurelio Galli
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biology
Keenan C. Taylor, Po Wei Kang, Panpan Hou, Nien-Du Yang, Georg Kuenze, Jarrod A. Smith, Jingyi Shi, Hui Huang, Kelli McFarland White, Dungeng Peng, Alfred L. George, Jens Meiler, Robert L. McFeeters, Jianmin Cui, Charles R. Sanders
Article
Peripheral Vascular Disease
Gail K. Adler, Gillian R. Murray, Adina F. Turcu, Hui Nian, Chang Yu, Carmen C. Solorzano, Robert Manning, Dungeng Peng, James M. Luther
Article
Peripheral Vascular Disease
James M. Luther, Dawei S. Wei, Kakali Ghoshal, Dungeng Peng, Gail K. Adler, Adina F. Turcu, Hui Nian, Chang Yu, Carmen C. Solorzano, Ambra Pozzi, Nancy J. Brown
Summary: Epoxyeicosatrienoic acids (EETs) are lipid signaling molecules generated by the action of CYP450s, with vasodilatory, anti-inflammatory, and insulin-enhancing effects. Treatment of primary aldosteronism led to an increase in EET concentrations, particularly 14,15-DHETs.
Meeting Abstract
Peripheral Vascular Disease
James M. Luther, Dungeng Peng, Anand Vaidya, Hayes McDonald, Kevin Schey, Gail K. Adler
Article
Endocrinology & Metabolism
Kakali Ghoshal, Xiyue Li, Dungeng Peng, John R. Falck, Raghunath Reddy Anugu, Manuel Chiusa, John M. Stafford, David H. Wasserman, Roy Zent, James M. Luther, Ambra Pozzi
Summary: In this study, researchers found that the administration of a water-soluble EET analog can improve insulin signaling in a genetic model of hepatic insulin resistance. The EET analog enhances hepatic insulin signaling, decreases expression of gluconeogenic genes, and increases expression of glycogenic genes. Mechanistically, the EET analog stabilizes membrane-associated IR beta and potentiates insulin signaling.
Article
Peripheral Vascular Disease
James M. Luther, Justina Ray, Dawei Wei, John R. Koethe, Latoya Hannah, Anthony DeMatteo, Robert Manning, Andrew S. Terker, Dungeng Peng, Hui Nian, Chang Yu, Mona Mashayekhi, Jorge Gamboa, Nancy J. Brown
Summary: The use of the sEH inhibitor GSK2256294 for 7 days effectively inhibits sEH activity in plasma, muscle, and adipose tissue, reducing the level of F2-isoprostanes. However, it does not improve insulin sensitivity or blood pressure.
Article
Rheumatology
Jorge Luis Gamboa, Daniel Carranza-Leon, Rachelle Crescenzi, Michael Pridmore, Dungeng Peng, Adriana Marton, Annette Oeser, Cecilia P. Chung, Jens Titze, Charles Michael Stein, Michelle Ormseth
Summary: This study found that patients with SLE have increased intermuscular adipose tissue (IMAT) accumulation, which is associated with greater fatigue and reduced physical activity. Interventions targeting muscle quality may be effective in alleviating fatigue in SLE patients.
LUPUS SCIENCE & MEDICINE
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Aparna Shekar, Nicholas Campbell, Jenny Aguilar, Dungeng Peng, Kevin Erreger, Heinrich Matthies, James Sutcliffe, Hassane Mchaourab, Aurelio Galli
Article
Biochemistry & Molecular Biology
Soojung Hahn, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim
Summary: This study utilized three-dimensional intestinal organoids to investigate the effects of metformin on inflammatory bowel disease (IBD) and found that metformin can enhance intestinal barrier function and reduce levels of inflammatory cytokines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
V. V. Sudarev, M. S. Gette, S. V. Bazhenov, O. M. Tilinova, E. V. Zinovev, I. V. Manukhov, A. I. Kuklin, Yu. L. Ryzhykau, A. V. Vlasov
Summary: This study investigated the self-assembly processes of ferritin-based protein complexes and obtained structurally characterized oligomeric states. These results provide new potential and opportunities for the application of ferritin in various fields.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Yalda Sabaghi, Farnaz Pourfarzad, Leila Zolghadr, Azita Bahrami, Tahereh Shojazadeh, Alireza Farasat, Nematollah Gheibi
Summary: p-Coumaric acid (p-CA) is a plant compound with anti-cancer activities. This study designed a nano-liposomal carrier containing p-CA to enhance its effectiveness against melanoma cells. The findings showed that the liposomal form of p-CA had a greater impact on the cells. Kinetic modeling indicated that the best fitting model was zero-order.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
M. D. Nazmul Hasan, Md Mahfuzur Rahman, Al Asmaul Husna, Nobuhiro Nozaki, Osamu Yamato, Naoki Miura
Summary: This study investigated the expression of ncRNAs other than miRNAs in different histologic subtypes of canine mammary gland tumors (MGT). Three aberrantly expressed ncRNAs were identified as potential biomarkers for differentiating MGT subtypes. YRNA and tRFs expression levels were found to be decreased in metastatic compared to primary MGT cell lines.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Seine A. Shintani
Summary: In this study, the researchers used signal analysis to study the instantaneous amplitude and phase of sarcomeric oscillations in skeletal muscle. They identified two types of oscillations, sarcomeric oscillations and sarcosynced oscillations, and visualized their behavior during propagating waves. The researchers discovered the presence of sarcomeric defect holes and sarcomeric collision holes, which are important indicators for understanding the oscillation properties of sarcomeres. This finding has important implications for improving our understanding of muscle function and its regulatory mechanisms.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Shuanglin Zhang, Yuzhong Jia, Guolan Ma, Yanyan Yang, Zhenzhen Cao, Antao Luo, Zefu Zhang, Shihan Li, Jie Wen, Hanfeng Liu, Jihua Ma
Summary: Bupleurum is an antiarrhythmic agent that may exert its effects by inhibiting L-type calcium channels.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Tomotaka Ohkubo, Yasuhiko Matsumoto, Hiroaki Sasaki, Kaoru Kinoshita, Yuki Ogasawara, Takashi Sugita
Summary: This study found that Citrobacter koseri inhibits the growth of Staphylococcus epidermidis, disrupting the balance between S. epidermidis and Staphylococcus aureus, and exacerbating inflammation in atopic dermatitis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Toshifumi Asano, Philipp Sasse, Takao Nakata
Summary: A Cre recombination-based fluorescent reporter system was developed to monitor cell-cell fusion. The system successfully detected the formation of multinuclear myotubes and placental syncytiotrophoblast. This tool could facilitate the study of cell-to-cell fusion.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Ke Shi, Yunlong Shan, Xiao Sun, Kuida Chen, Qiong Luo, Qiang Xu
Summary: This study found that low expression of TP53INP2 is associated with poor survival in colorectal cancer (CRC) patients. As the malignancy of CRC progresses, TP53INP2 expression gradually decreases. Knockdown of TP53INP2 promotes CRC cell proliferation and tumor growth. Mechanistically, TP53INP2 deficiency decreases phosphorylation of beta-catenin, leading to increased accumulation and enhanced nuclear translocation and transcriptional activity. Additionally, TP53INP2 sequesters TIM50, inhibiting its activation of beta-catenin. In conclusion, downregulation of TP53INP2 promotes CRC progression by activating beta-catenin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Martina Rossi, Fabio Tomaselli, Alejandro Hochkoeppler
Summary: Oligomeric enzymes are known for their higher catalytic rates compared to monomeric enzymes, but the extent of additivity in their activity is still not well understood. This study used tetrameric rabbit lactate dehydrogenase as a model to examine the kinetics of its catalytic action. Surprisingly, when the concentration of the limiting reactant exceeded that of a single subunit, there was a significant slowdown in the enzyme's conformational rearrangements.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Amin Sahraei, Mohammad Javad Shamsoddini, Fakhrossadat Mohammadi, Leila Hassani
Summary: This study explored the inhibitory effects of gallium curcumin, indium curcumin, and vanadyl curcumin on the amyloid fibrillation of hen egg white lysozyme, as well as the binding interactions of these metal complexes with the enzyme. The results showed that indium curcumin and vanadyl curcumin exhibited higher binding affinities and stronger inhibitory effects on amyloid fibrillation compared to gallium curcumin.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Takahiro Sasaki, Yoshiki Kuse, Shinsuke Nakamura, Masamitsu Shimazawa
Summary: PGRN deficiency plays a significant role in cardiac remodeling and arrhythmias post-myocardial infarction (MI), potentially by promoting metabolic abnormalities in macrophages.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Hongwei Zhao, Yiqiang Li, Yibo Zhang, Chi Zhang
Summary: Electrical brain stimulation technology is commonly used to treat brain neurological disorders, but it can cause side effects. This study investigated the impact of electric fields on nerve fibers and revealed the possible origin of side effects. The findings provide guidance for selecting electrical parameters in clinical stimulation therapy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Julia S. Scott, Lake-Ee Quek, Andrew J. Hoy, Johannes V. Swinnen, Zeyad D. Nassar, Lisa M. Butler
Summary: The fatty acid elongation enzyme ELOVL5 plays a critical role in promoting metastasis in prostate cancer. Knocking down ELOVL5 leads to the accumulation of malonyl-CoA, which inhibits fatty acid oxidation in mitochondria. This study highlights the importance of fatty acid elongation in regulating cell viability and provides a potential target for prostate cancer treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)
Article
Biochemistry & Molecular Biology
Zan Zhou, Wen-jun Jiang, Li Li, Jun-qiang Si
Summary: This study investigates the effect of noise exposure on cognitive function in mice and explores the underlying molecular mechanisms. The findings suggest that noise exposure leads to increased inflammation, increased phosphorylation of Tau protein, and decreased levels of postsynaptic density protein, resulting in cognitive impairment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2024)