Review
Oncology
Kangzhe Xie, Keely Tan, Matthew J. Naylor
Summary: Prostate cancer, the second most diagnosed cancer among men, is influenced by androgen resistance and dysregulation of transcription factors. Recent research has identified the potential of using transcriptional regulators as therapeutic targets for the management of prostate cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chun-Yi Yang, Chiu-Fen Yang, Xiao-Fang Tang, Luciana E. S. F. Machado, Jai Prakash Singh, Wolfgang Peti, Chien-Sheng Chen, Tzu-Ching Meng
Summary: Reactive oxygen species (ROS) can oxidize the active-site cysteine residue of protein tyrosine phosphatases (PTPs), leading to their irreversible oxidation. In this study, it was found that the active-site cysteine (Cys215) of endogenous PTP1B is sulfonated, which triggers its conformational change and subsequent ubiquitination and degradation. Furthermore, the E3 ligase Cullin1 interacts with the sulfonated PTP1B and is essential for its oxidation-dependent ubiquitination and degradation. These findings uncover a novel mechanism that regulates the turnover of endogenous PTP1B through the engagement of the ubiquitin-proteasome system.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Filipp Bezold, Johannes Scheffer, Philipp Wendering, Zahra Razaghi-Moghadam, Jonathan Trauth, Bastian Pook, Hagen Nusshaer, Sophia Hasenjaeger, Zoran Nikoloski, Lars-Oliver Essen, Christof Taxis
Summary: Dynamic metabolic engineering is a strategy to switch key metabolic pathways in microbial cell factories to increase production of valuable chemicals. In this study, optogenetic intervention was used to arrest the cell cycle of budding yeast, resulting in increased production of terpenoid and nucleoside analog. Proteomic analysis revealed significant changes in metabolic key enzymes, and integration of the data in metabolic models demonstrated modulation of fluxes associated with product synthesis. These results highlight the potential of optogenetically triggered cell cycle intervention in improving compound yields in cellular factories.
METABOLIC ENGINEERING
(2023)
Review
Cell Biology
Jason Q. Tang, Mary M. Marchand, Gianluca Veggiani
Summary: Protein turnover, regulated by the ubiquitin-proteasome system (UPS), is important for cellular homeostasis. Dysregulation of the UPS is associated with diseases and UPS enzymes are attractive therapeutic targets. However, redundancies of UPS enzymes make it challenging to identify precise drug targets. Engineered ubiquitin has emerged as a promising alternative to guide the development of small molecules targeting novel surfaces.
Article
Biochemistry & Molecular Biology
Apoorvi Tyagi, Saba Haq, Suresh Ramakrishna
Summary: Reactive oxygen species (ROS) play a dual role in cancer, with low levels being beneficial while excessive accumulation can lead to cancer progression. Recent studies have shown that deubiquitinating enzymes (DUBs) are regulated by ROS, with the oxidation of catalytic cysteine leading to reversible inactivation, offering potential new insights for anticancer therapeutics.
Review
Pharmacology & Pharmacy
Agata Kodron, Ben Hur Mussulini, Iwona Pilecka, Agnieszka Chacinska
Summary: Proteasome dysfunction can lead to protein toxicity and mitochondrial dysfunction, while mitochondrial impairment can cause protein oxidation and misfolding leading to proteasome overload.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Angela Rocchi, Hassen S. Wollebo, Kamel Khalili
Summary: Protein quality control is crucial for maintaining proteostasis in eukaryotes under changing conditions. Bag3 plays a key role in this process and excessive activity of Bag3-HSP70 has been linked to sustained and propagated cancers. Targeting Bag3 is essential for the successful treatment of glioblastoma, a highly recurrent cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yan-Chi Li, Song-Wang Cai, Yu-Bin Shu, Mei-Wan Chen, Zhi Shi
Summary: The process of protein ubiquitination and deubiquitination, especially the involvement of USP15, play crucial roles in maintaining protein stability, regulating signal pathways, and tumorigenesis. However, the importance and complexity of USP15 in pathological processes remain unclear.
Review
Oncology
Grazia R. Tundo, Diego Sbardella, Francesco Oddone, Anna A. Kudriaeva, Pedro M. Lacal, Alexey A. Belogurov, Grazia Graziani, Stefano Marini
Summary: The immunoproteasome plays a crucial role in antigen presentation and its modulation presents promising research opportunities. Immunotherapy has shown significant advancements, however, a broader understanding of cancer cell antigen processing dynamics is still required for further improvements.
Article
Biochemistry & Molecular Biology
Liang Ren, Bei Xu, Jiadai Xu, Jing Li, Jifeng Jiang, Yuhong Ren, Peng Liu
Summary: A UBBRS risk score model was established by selecting UPPGs associated with overall survival of MM patients, which can predict the survival of MM patients and identify patients who would benefit more from PIs treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Cong Ma, Ronghui Yu, Junhong Li, Jiashuo Chao, Ping Liu
Summary: Osteoporosis is a common bone disease that increases bone fragility and susceptibility to fractures. With an aging population, it has become a growing public health problem. The pathogenesis of osteoporosis is still unclear, and effective interventions are limited. Therefore, exploring new targets for pharmacological interventions is of great clinical value.
AGEING RESEARCH REVIEWS
(2023)
Article
Neurosciences
Kayla Farrell, Madeline Musaus, Shaghayegh Navabpour, Kiley Martin, W. Keith Ray, Richard F. Helm, Timothy J. Jarome
Summary: The study revealed differences in protein targets of degradation process in the amygdala between male and female rats following fear conditioning, suggesting possible sex specificity. K48 polyubiquitin may contribute to fear memory formation by degrading various proteins involved in the process.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Immunology
Monica Roman-Trufero, Holger W. Auner, Claire M. Edwards
Summary: Multiple myeloma is an incurable cancer of plasma cells that primarily affects the bone marrow. This article discusses the major metabolic characteristics of plasma cells and myeloma cells, their roles in disease progression, and potential therapeutic applications. It also explores the complex relationship between myeloma cells and the bone marrow microenvironment.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Oncology
Abdulkadir Elmas, Amaia Lujambio, Kuan-lin Huang
Summary: In this study, proteogenomic analyses were performed on hepatocellular carcinoma (HCC) tumors, revealing overexpressed protein targets that have therapeutic potential even in the absence of clinically actionable mutations. The study demonstrates the importance of proteomics approaches in advancing precision medicine for cancer types lacking druggable mutations.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Thiago Seraphim, Nardin Nano, Yiu Wing Sunny Cheung, Siripat Aluksanasuwan, Carolina Colleti, Yu-Qian Mao, Vaibhav Bhandari, Gavin Young, Larissa Holl, Sadhna Phanse, Yuliya Gordiyenko, Daniel R. Southworth, Carol Robinson, Visith Thongboonkerd, Lisandra M. Gava, Julio C. Borges, Mohan Babu, Leandro R. S. Barbosa, Carlos H. Ramos, Philipp Kukura, Walid A. Houry
Summary: The R2TP complex, formed by RUVBL1 and RUVBL2 ATPases, associates with PIH1D1 and RPAP3 proteins and plays a role in promoting the formation of macromolecular complexes. RPAP3 is identified as the central subunit of R2TP, linking PIH1D1 and RUVBL1/2. The study provides insights into the structure and function of the R2TP complex.
Article
Biology
Sunisa Yoodee, Chadanat Noonin, Kanyarat Sueksakit, Rattiyaporn Kanlaya, Sakdithep Chaiyarit, Paleerath Peerapen, Visith Thongboonkerd
Summary: Using label-free quantitative proteomics, this study identified significantly altered secreted proteins from COM-exposed macrophages, suggesting their potential role in renal fibrogenesis in kidney stone disease.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Paleerath Peerapen, Kanyarat Sueksakit, Wanida Boonmark, Sunisa Yoodee, Visith Thongboonkerd
Summary: Loss of ARID1A is associated with higher grade of colorectal cancer. In this study, knockdown of ARID1A resulted in decreased cell death and senescence, enhanced cell proliferation, chemoresistance and invasion. Additionally, ARID1A knockdown led to the formation of polyploid giant cancer cells, increased cell aggregation and secretion of vascular endothelial growth factor (VEGF).
Article
Medicine, Research & Experimental
Paleerath Peerapen, Wanida Boonmark, Visith Thongboonkerd
Summary: This study investigated the protective effects and mechanisms of trigonelline against kidney stone formation. The results showed that trigonelline can reduce stone formation by inhibiting crystallization, crystal growth, and crystal-cell adhesion. Additionally, trigonelline downregulated crystal receptors on the apical membranes of renal tubular cells.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Chadanat Noonin, Paleerath Peerapen, Sunisa Yoodee, Chompunoot Kapincharanon, Rattiyaporn Kanlaya, Visith Thongboonkerd
Summary: This study clarifies the inhibitory roles of native human urinary THP in calcium oxalate monohydrate (COM) kidney stone formation. THP reduces COM crystal size, inhibits crystal growth and aggregation, and prevents crystal-cell adhesion. These inhibitory effects are predominantly mediated via the high affinity of THP with calcium ions.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Rattiyaporn Kanlaya, Chompunoot Kapincharanon, Kedsarin Fong-ngern, Visith Thongboonkerd
Summary: This study investigated the potential of epigallocatechin-3-gallate (EGCG) to reverse epithelial-mesenchymal transition (EMT) and restore normal cell morphology. The results demonstrated that EGCG effectively reversed EMT and inhibited tumor and fibrosis.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Article
Toxicology
Chanettee Chanthick, Visith Thongboonkerd
Summary: This study found that hyaluronic acid promotes the formation of calcium oxalate kidney stones by enhancing crystal growth, adhesion to cells, and invasion through the extracellular matrix. These findings provide an explanation for the higher levels of hyaluronic acid in the urine of stone patients.
TOXICOLOGY IN VITRO
(2022)
Article
Biochemistry & Molecular Biology
Rattiyaporn Kanlaya, Visith Thongboonkerd
Summary: This study demonstrates that persistent infection by E. coli may contribute to COM metabolic stone formation by translocation of ezrin to apical membranes, thereby promoting COM crystal-cell adhesion.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sunisa Yoodee, Paleerath Peerapen, Sirikanya Plumworasawat, Visith Thongboonkerd
Summary: This study found that heat-shock protein 90 (HSP90) and its four functional domains play important roles in the formation of kidney stones, promoting the crystallization, growth, aggregation, adhesion onto renal cells, and invasion through the extracellular matrix (ECM) of calcium oxalate monohydrate (COM) crystals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Visith Thongboonkerd, Rattiyaporn Kanlaya
Summary: Exosomes are nanoscale vesicles derived from late endosomes and released from cells. They selectively encapsulate biomolecules and play roles in cell-cell communication. In kidney diseases, exosomes have divergent roles in pathogenesis, diagnostics, prognostics, and therapeutics.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sakdithep Chaiyarit, Visith Thongboonkerd
Summary: The research reveals that oxidative modification can reverse the modulatory activity of the urinary protein uromodulin (UMOD), promoting calcium oxalate stone formation. Oxidized forms of UMOD facilitate CaOx crystallization and crystal growth, while having no effect on crystal aggregation.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Medicine, Research & Experimental
Sudarat Hadpech, Visith Thongboonkerd
Summary: CyPA is an immunophilin widely expressed in various cell types and tissues, with higher expression in proximal tubular epithelial cells in the kidney. Changes in CyPA expression and secretion play important roles in kidney diseases. Urinary CyPA shows promise as a diagnostic/prognostic marker in several kidney diseases. Understanding the theranostic roles of CyPA in kidney diseases may offer insights for designing new therapeutic interventions and prevention strategies.
Review
Medicine, Research & Experimental
Chadanat Noonin, Visith Thongboonkerd
Summary: The inflammasome is a complex of proteins in the cytoplasm of cells activated by infectious and non-infectious stimuli, while exosomes are extracellular vesicles that play important roles in intercellular communication. The review discusses the interaction between exosomes and inflammasomes in inflammatory responses, highlighting the effects of inflammasome activation on exosomal secretion. Additionally, it explores the dual effects of exosomes on inhibiting and promoting inflammasome activation, and provides insights into the therapeutic potential of exosomes in human diseases.
Article
Cell Biology
Uta Erdbrugger, Charles J. Blijdorp, Irene V. Bijnsdorp, Francesc E. Borras, Dylan Burger, Benedetta Bussolati, James Brian Byrd, Aled Clayton, James W. Dear, Juan M. Falcon-Perez, Cristina Grange, Andrew F. Hill, Harry Holthofer, Ewout J. Hoorn, Guido Jenster, Connie R. Jimenez, Kerstin Junker, John Klein, Mark A. Knepper, Erik H. Koritzinsky, James M. Luther, Metka Lenassi, Janne Leivo, Inge Mertens, Luca Musante, Eline Oeyen, Maija Puhka, Martin E. van Royen, Catherine Sanchez, Carolina Soekmadji, Visith Thongboonkerd, Volkert van Steijn, Gerald Verhaegh, Jason P. Webber, Kenneth Witwer, Peter S. T. Yuen, Lei Zheng, Alicia Llorente, Elena S. Martens-Uzunova
Summary: Urine is commonly used for clinical diagnosis and biomedical research, and the discovery of extracellular vesicles (EV) in urine has opened a new scientific field. However, methods for isolating and characterizing urinary extracellular vesicles (uEVs) need further optimization and standardization to advance scientific research and translation into clinical practice. Recommendations for improved rigor, reproducibility, and interoperability in uEV research are provided to address current challenges and gaps in the field.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Review
Biochemistry & Molecular Biology
Liliana Moreira-Costa, Antonio S. Barros, Andre P. Lourenco, Adelino F. Leite-Moreira, Rita Nogueira-Ferreira, Visith Thongboonkerd, Rui Vitorino
Summary: Exosomes as complementary prospective biomarkers of cardiovascular diseases have drawn attention, but their exact role in CVDs is not fully elucidated. Studies suggest that certain exosomal miRNAs and proteins may serve as potential biomarkers for cardiovascular diseases, aiding in diagnosis and prognosis assessment.