Article
Biochemistry & Molecular Biology
Ana C. Matias, Joao Matos, R. Juergen Dohmen, Paula C. Ramos
Summary: While assembly of the 20S proteasome core particle (CP) in prokaryotes occurs spontaneously, in eukaryotes, dedicated assembly chaperones are required for efficient CP assembly. This study found that in S. cerevisiae, the CP subunits alpha 1, alpha 2, and alpha 4 form independent small complexes instead of a complete alpha-ring. The presence of Hsp70 and Hsp110 chaperones was detected in these complexes, and they were found to cooperate in promoting the folding and assembly of alpha subunits with other CP subunits.
Review
Cell Biology
Sumit Kinger, Ankur Rakesh Dubey, Prashant Kumar, Yuvraj Anandrao Jagtap, Akash Choudhary, Amit Kumar, Vijay Kumar Prajapati, Rohan Dhiman, Amit Mishra
Summary: Amyotrophic lateral sclerosis (ALS) is a neuronal degenerative condition caused by the accumulation of mutant aberrantly folded proteins. The involvement of chaperones in ALS pathogenesis is not thoroughly understood, making it challenging to develop effective treatments for the disease.
Article
Biochemistry & Molecular Biology
Aitor Franco, Jorge Cuellar, Jose Angel Fernandez-Higuero, Igor de la Arada, Natalia Orozco, Jose M. Valpuesta, Adelina Prado, Arturo Muga
Summary: The aggregation of alpha-synuclein in synucleinopathies is regulated by post-translational modifications, with proteolysis at both the N- and C-terminal regions affecting the disassembly of toxic amyloids by chaperones. Truncation-driven aggregate clumping impairs the mechanical action of chaperones, leading to exacerbated toxicity and higher propensity to deposit in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Ana Gonzalez-Garcia, Antonio Garrido, Ana C. Carrera
Summary: Genetic alterations in the PI3-kinase/PTEN pathway are common in cancer cells. Current efforts to treat PTEN-dependent tumors mainly focus on PI3-kinase inhibition, but modulating PTEN post-translational modifications could provide alternative therapeutic strategies.
Article
Pharmacology & Pharmacy
Magdalena Zabinska, Lidia Gaffke, Patrycja Bielanska, Magdalena Podlacha, Estera Rintz, Zuzanna Cyske, Grzegorz Wegrzyn, Karolina Pierzynowska
Summary: Mucopolysaccharidoses (MPS) are rare genetic disorders characterized by the accumulation of glycosaminoglycans (GAGs) in lysosomes due to mutations in lysosomal enzymes. This study found significantly reduced levels of chaperone proteins Hsp70 and Hsp40 in MPS cells. Lowering GAG levels did not normalize chaperone levels, suggesting that reduced chaperone levels may contribute to the low activity of lysosomal enzymes in MPS.
Review
Biochemistry & Molecular Biology
Henrieta Havalova, Gabriela Ondrovicova, Barbora Keresztesova, Jacob A. Bauer, Vladimir Pevala, Eva Kutejova, Nina Kunova
Summary: Heat shock proteins (HSPs) are found in all domains of life, particularly in mitochondria where they play crucial roles in maintaining organelle function and health. The human mitochondrial HSP70 chaperone system consists of mtHSP70 or mortalin and three co-chaperones, which work together to stabilize and import nuclear gene products and regulate protein folding functions. Dysregulation of these molecular chaperones is often linked to neurological disorders, genetic diseases, and cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Dimitrios Tsikas
Summary: Lysine residues in proteins undergo various chemical modifications, including carbonylation by glyoxal (GO) and methylglyoxal (MGO). Malondialdehyde (MDA) is another carbonyl species formed enzymatically and nonenzymatically. These carbonyl species can occur in free forms or be adducted to proteins, particularly lysine residues. MDA is commonly used as a biomarker of lipid peroxidation, with plasma and serum being the most frequently analyzed samples. However, preanalytical factors, such as artificial MDA formation in lipid-rich samples, can greatly affect MDA concentrations.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Benjamin C. Orsburn, Yuting Yuan, Namandje N. Bumpus
Summary: Single-cell proteomics is a powerful tool for studying cellular heterogeneity and quantifying post-translational modifications. The authors developed a method with improved protein sequence coverage and demonstrated its application in characterizing the effects of inhibitor treatment in single human cells. This approach allows for the detection of multiple classes of post-translational modifications and provides insight into cell-to-cell variability in drug response that is missed by traditional proteomics.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Sergio Enriquez-Flores, Ignacio De la Mora-De la Mora, Itzhel Garcia-Torres, Luis A. Flores-Lopez, Yoalli Martinez-Perez, Gabriel Lopez-Velazquez
Summary: Cancer is a group of diseases characterized by uncontrolled cellular growth. It is a major cause of death globally, with a growing incidence and mortality rate, especially in developing countries. Various treatments, such as chemotherapy, immunotherapy, and organ transplantation, are currently used but can lead to severe side effects. Increased glycolytic activity is a hallmark of cancer cells, and post-translational modifications of triosephosphate isomerase, an enzyme involved in glycolysis, offer a potential target for effective cancer treatment.
Review
Veterinary Sciences
Tong Zhou, Mingshu Wang, Anchun Cheng, Qiao Yang, Bin Tian, Ying Wu, Renyong Jia, Shun Chen, Mafeng Liu, Xin-Xin Zhao, Xuming Ou, Sai Mao, Di Sun, Shaqiu Zhang, Dekang Zhu, Juan Huang, Qun Gao, Yanling Yu, Ling Zhang
Summary: This article mainly describes the viral protein kinases and their mechanisms of regulating viral protein function through phosphorylation. The study of post-translational modification of viral proteins is of great significance for understanding viral infection mechanisms and developing antiviral treatment.
VETERINARY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Liqing Hu, Cancan Sun, Justin M. Kidd, Jizhong Han, Xianjun Fang, Hongtao Li, Qingdai Liu, Aaron E. May, Qianbin Li, Lei Zhou, Qinglian Liu
Summary: In this study, the authors provide proof-of-principle evidence supporting fungal Hsp110s as targets for the development of new antifungal drugs. They identify a compound called 2H that inhibits the activities of Msi3 and the growth of Candida albicans. The authors propose 2H and related compounds as promising leads for the development of new antifungals and for studying the molecular mechanisms of Hsp110s.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Surya Kannan, Serhiy Souchelnytskyi
Summary: This study reviews novel post-translational modifications (PTMs) of human serum albumin, including phosphorylation, glycation, methylation, carbonylation, and acetylation. The potential impact of these modifications on albumin functions is discussed, highlighting their importance in medical applications.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Juan Facundo Chrestia, Ornella Turani, Noelia Rodriguez Araujo, Guillermina Hernando, Maria del Carmen Esandi, Cecilia Bouzat
Summary: Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central and peripheral nervous system and play crucial roles in vital physiological processes. Post-translational modifications (PTMs) have been shown to regulate different aspects of nAChR life cycle, but our knowledge in this field is still limited and many important aspects remain unknown.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Matthias M. Schneider, Saurabh Gautam, Therese W. Herling, Ewa Andrzejewska, Georg Krainer, Alyssa M. Miller, Victoria A. Trinkaus, Quentin A. E. Peter, Francesco Simone Ruggeri, Michele Vendruscolo, Andreas Bracher, Christopher M. Dobson, F. Ulrich Hartl, Tuomas P. J. Knowles
Summary: Molecular chaperones play a role in maintaining cellular protein homeostasis by assisting in protein folding and preventing amyloid formation. Chaperones from the Hsp70 family can disaggregate protein aggregates, including amyloids, with the Hsc70-DnaJB1-Apg2 system directly removing single molecules from fibril ends.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Yun Li, Hong Yang, Tianhan He, Liang Zhang, Chao Liu
Summary: Cav1.2 plays a crucial role in neurodegenerative diseases, but the regulation of its activity remains incompletely understood. The repurposing of DHP drugs may offer potential therapeutic strategies, but further research is needed.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Jose-Emilio Sanchez-Aparicio, Laura Tiessler-Sala, Lorea Velasco-Carneros, Lorena Roldan-Martin, Giuseppe Sciortino, Jean-Didier Marechal
Summary: This study introduces a metal-binding site predictor, BioMetAll, based on the geometric organization of the protein backbone. Through statistical analysis of geometric descriptors of the backbone, successful benchmarking on over 90 metal-binding X-ray structures was achieved, highlighting its value in predicting metal-binding sites.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Oncology
Leire Dublang, Jarl Underhaug, Marte Flydal, Lorea Velasco-Carneros, Jean-Didier Marechal, Fernando Moro, Maria Dolores Boyano, Aurora Martinez, Arturo Muga
Summary: High levels of Heat shock proteins (Hsps) are often associated with poor prognosis, tumor progression, and resistance to treatment in specific cancers. This study demonstrates the potential of using the small chemical compound pinaverium bromide, originally used for gastrointestinal disorders, as an antitumor drug by targeting Hsp70 and Hsp110 families. The compound inhibits the substrate remodeling ability of the Hsp70 system, specifically targeting melanoma cells, and shows promise as a novel therapeutic approach for cancer treatment.
Review
Cell Biology
Aitor Franco, Lorea Velasco-Carneros, Naiara Alvarez, Natalia Orozco, Fernando Moro, Adelina Prado, Arturo Muga
Summary: Neurodegenerative diseases are increasingly recognized as leading causes of global deaths, especially with the aging population. Recent studies have shown that the chaperone system can disassemble protein aggregates associated with neurodegenerative diseases, potentially significant for the development of new therapies.