Article
Biochemistry & Molecular Biology
Dan Wu, Tao Liu
Summary: Understanding post-translational modifications is crucial for manipulating physiological processes in eukaryotes. Genetic code expansion technology has been used to investigate the roles of these modifications, and can be combined with synthetic biology to create genetically modified organisms. This article discusses the applications, limitations, and future perspectives of genetic code expansion technology for studying post-translational modifications, as well as the implications for genetically modified organisms.
Article
Chemistry, Medicinal
Yanli Liu, Zitong Zhao, Yunyang Song, Yifeng Yin, Fanghui Wu, Hui Jiang
Summary: This article investigates the post-translational modification mechanism of a protein in mollusk venom and finds that prolyl 4 hydroxylase catalyzes the hydroxylation of proline by recognizing the propeptide of mu-PIIIA. This finding provides a new approach for synthesizing multi-modified mollusk venom proteins with pharmacological activity.
Review
Cell Biology
Mingyue Zheng, Guoxiang Jin, Zhongjun Zhou
Summary: Lamins, ancient intermediate filament proteins, are functionally regulated by post-translational modifications, contributing to various biological functions. Deregulation of lamins is associated with abnormal nuclear morphology and chromatin disorganization, leading to diseases. Understanding these modifications provides new insights into the molecular mechanisms underlying diseases and potential therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Yanfeng Wang, Feng Wang
Summary: Post-translational modifications like ubiquitination play crucial roles in regulating biological processes in eukaryotes, with DUBs being key enzymes that control ubiquitin-related pathways. Dysregulation of DUBs can lead to various diseases. Phosphorylation is the most extensively studied post-translational modification of DUBs, influencing their function and activity.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maxence S. Vincent, Benjamin Ezraty
Summary: Methionine, a sulfur-containing residue in proteins, is prone to oxidation which can damage or activate protein function. Many bacteria possess enzymatic systems to reduce oxidized methionine, highlighting its reversible post-translational modification role. This review examines recent examples of methionine oxidation leading to protein loss or gain of function, and speculates on its role as a multilayer endogenous antioxidant system and its potential consequences for bacterial virulence.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemical Research Methods
Vivek Sarohi, Trayambak Basak
Summary: Myocardial infarction (MI) leading to heart failure is responsible for almost 85% of deaths associated with cardiovascular diseases. Stenting is a common technique used to maintain proper blood flow in the myocardium's coronary circulation. However, both bare metal stents (BMS) and drug-eluting stents (DES) can cause neointima formation and restenosis. This study analyzed the post-translational modifications (PTMs) of COL1A1 in neointima ECM and found significant alterations in PTM levels, suggesting their important role in ECM remodeling during stent-induced neointima formation in MI patients.
JOURNAL OF PROTEOMICS
(2023)
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
Biochemistry & Molecular Biology
Sharon L. Campbell, Mark R. Philips
Summary: Mutations in RAS genes are the most common driving force behind cancer development. RAS proteins, acting as binary molecular switches, control cellular growth through a complex signaling pathway. In addition to nucleotide-binding properties, RAS proteins are also regulated by numerous post-translational modifications, which are currently a high priority for drug discovery research in the field of RAS biology.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Qibin Wu, Zhenxiang Li, Jingtao Yang, Fu Xu, Xueqin Fu, Liping Xu, Chuihuai You, Dongjiao Wang, Yachun Su, Youxiong Que
Summary: This study reports the first comprehensive analysis of protein lysine acetylation, 2-hydroxyisobutyrylation, and lysine lactylation in sugarcane. These post-translational modifications were found to be involved in energy metabolism and stress response. The results provide new insights into the molecular mechanisms of protein PTMs in sugarcane.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
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.
Article
Biochemistry & Molecular Biology
Leonard A. Daly, Philip J. Brownridge, Michael Batie, Sonia Rocha, Violaine See, Claire E. Eyers
Summary: Cellular adaptation to low-oxygen environments is partially mediated by hypoxia-inducible factors (HIFs), whose stability and activity are regulated by post-translational modifications (PTMs) and protein-protein interactions. Hypoxia alters the complexity and composition of HIF alpha protein interaction networks, particularly for HIF-2 alpha, with the networks enriched for mitochondrial proteins. Additionally, both HIF alpha isoforms undergo heavy covalent modifications, with a majority of newly identified PTMs exhibiting oxygen dependency.
Article
Multidisciplinary Sciences
Masahiko Terajima, Yuki Taga, Tomoyuki Nakamura, Hou-Fu Guo, Yukako Kayashima, Nobuyo Maeda-Smithies, Kshitij Parag-Sharma, Jeong Seon Kim, Antonio L. Amelio, Kazunori Mizuno, Jonathan M. Kurie, Mitsuo Yamauchi
Summary: This study investigated the role of LH2 in collagen stability, organization, and mineralization using LH2-null MC3T3 cells. The results demonstrated that LH2 is involved in the hydroxylation of telopeptidyl Lys residues of collagen and affects collagen solubility, fibril diameter, and mineralization.
SCIENTIFIC REPORTS
(2022)
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
Chemistry, Multidisciplinary
Suze Ma, Heng Chen, He Li, Xinjian Ji, Zixin Deng, Wei Ding, Qi Zhang
Summary: The study reveals a enzyme named three-residue cyclophane forming enzyme (3-CyFE) exhibiting remarkable catalytic promiscuity, producing cyclophane and aminomalonate. Bioinformatic analysis indicates that 3-CyFEs have evolved from a common ancestor with anaerobic sulfatase maturases (anSMEs) and share a similar set of catalytic residues.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Lynsay Blake, Martin J. Cann
Summary: Carbon dioxide plays a crucial role in various life processes, regulating cellular reactions, transport, maintenance, and behavior. Protein carbamate modification, mediated by carbon dioxide, is a mechanism that may alter protein function and participate in sensing and signaling.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Pranvera Sadiku, Joseph A. Willson, Ellise M. Ryan, David Sammut, Patricia Coelho, Emily R. Watts, Robert Grecian, Jason M. Young, Martin Bewley, Simone Arienti, Ananda S. Mirchandani, Manuel A. Sanchez Garcia, Tyler Morrison, Ailing Zhang, Leila Reyes, Tobias Griessler, Privjyot Jheeta, Gordon G. Paterson, Christopher J. Graham, John P. Thomson, Kenneth Baillie, A. A. Roger Thompson, Jessie-May Morgan, Abel Acosta-Sanchez, Veronica M. Darde, Jordi Duran, Joan J. Guinovart, Gio Rodriguez-Blanco, Alex Von Kriegsheim, Richard R. Meehan, Massimiliano Mazzone, David H. Dockrell, Bart Ghesquiere, Peter Carmeliet, Moira K. B. Whyte, Sarah R. Walmsley
Summary: Recent research has shown that neutrophils can effectively survive and kill bacteria in injured and infected tissues by generating intracellular glycogen stores through gluconeogenesis and glycogenesis. Additionally, reduced glycogen cycling in neutrophils from patients with chronic obstructive pulmonary disease may be associated with impaired function.
Article
Cardiac & Cardiovascular Systems
Joao P. Monteiro, Julie Rodor, Axelle Caudrillier, Jessica P. Scanlon, Ana-Mishel Spiroski, Tatiana Dudnakova, Beatrice Pfluger-Muller, Alena Shmakova, Alex von Kriegsheim, Lin Deng, Richard S. Taylor, John R. Wilson-Kanamori, Shiau-Haln Chen, Kevin Stewart, Adrian Thomson, John D. McClure, Jean Iynikkel, Patrick W. F. Hadoke, Laura Denby, Angela C. Bradshaw, Paola Caruso, Nicholas W. Morrell, Jason C. Kovacic, Igor Ulitsky, Neil C. Henderson, Andrea Caporali, Matthias S. Leisegang, Ralf P. Brandes, Andrew H. Baker, Tijana Mitic
Summary: This study identified a novel lncRNA transcriptional profile associated with EndMT and highlighted the crucial role of MIR503HG loss in EndMT and its relevance to pulmonary hypertension. The findings suggest that MIR503HG may have therapeutic potential in treating EndMT-related conditions such as pulmonary hypertension. Additionally, the study revealed an interaction between MIR503HG and PTBP1, pointing to a potential mechanism by which MIR503HG mediates its effects on EndMT.
CIRCULATION RESEARCH
(2021)
Article
Multidisciplinary Sciences
Joseph J. Rossi, Jill A. Rosenfeld, Katie M. Chan, Haley Streff, Victoria Nankivell, Daniel J. Peet, Murray L. Whitelaw, David C. Bersten
Summary: Aberrations in the NPAS3 and NPAS4 genes can potentially disrupt protein function and lead to developmental delay or intellectual disability. These variants result in a loss of transcriptional activity and impaired interaction with specific partner proteins.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Andrei V. Grinchenko, Alex von Kriegsheim, Nikita A. Shved, Anna E. Egorova, Diana V. Ilyaskina, Tatiana D. Karp, Nikolay V. Goncharov, Irina Y. Petrova, Vadim V. Kumeiko
Summary: C1q domain-containing (C1qDC) proteins are biopolymers involved in immune response by recognizing patterns in a lectin-like manner. MkC1qDC, a new protein from Modiolus kurilensis, displays antibacterial properties and binds to various saccharides in a Ca2+-dependent manner.
Article
Multidisciplinary Sciences
Liang-Cui Chu, Pedro Arede, Wei Li, Erika C. Urdaneta, Ivayla Ivanova, Stuart W. McKellar, Jimi C. Wills, Theresa Frohlich, Alexander von Kriegsheim, Benedikt M. Beckmann, Sander Granneman
Summary: RNA-binding proteins play a crucial role in controlling gene expression. This study identifies hundreds of RNA-binding proteins in methicillin-resistant Staphylococcus aureus (MRSA) and demonstrates that a major transcription factor binds RNAs near intrinsic transcription terminators using its helix-turn-helix domain.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Emily L. Button, Joseph J. Rossi, Daniel P. McDougal, John B. Bruning, Daniel J. Peet, David C. Bersten, Jill A. Rosenfeld, Murray L. Whitelaw
Summary: SIM2 is a neuron-enriched transcription factor crucial for mammalian survival. This study identified several human variants of SIM2 that are associated with disabilities and validated their potential contribution to pathology.
BIOCHEMICAL JOURNAL
(2022)
Article
Biology
Lewis Macdonald, Gillian C. Taylor, Jennifer Margaret Brisbane, Ersi Christodoulou, Lucy Scott, Alex von Kriegsheim, Janet Rossant, Bin Gu, Andrew J. Wood
Summary: Researchers have developed a genetic engineering method using CRISPR technology to efficiently degrade endogenous proteins in vivo, and found that degradation kinetics depend on the dosage of the protein, ligand, and substrate receptor. Applying this method to the study of key regulators of cell division, they discovered that these regulators are essential for cell division in precursor lymphocytes.
Article
Genetics & Heredity
Jennifer Lennon, Petra zur Lage, Alex von Kriegsheim, Andrew P. Jarman
Summary: Axonemal dynein motors are complex protein complexes that drive ciliary movement. The Drosophila homologues of DNAAF4 and DNAAF6, CG14921/Dnaaf4 and CG5048/Dnaaf6, are found to associate in a complex similar to R2TP and play a crucial role in dynein assembly during the development of motile cilia.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Ana Martin-Vega, Laura Ruiz-Peinado, Rocio Garcia-Gomez, Ana Herrero, Dalia de la Fuente-Vivas, Swetha Parvathaneni, Ruben Caloto, Marta Morante, Alex von Kriegsheim, Xose R. Bustelo, David B. Sacks, Berta Casar, Piero Crespo
Summary: RAS-ERK pathway signals are regulated by scaffold proteins, and it is revealed that scaffold proteins can interact with each other and undergo phosphorylation reactions. The trans-phosphorylation process participates in KSR1-regulated adipogenesis and the cytotoxicity exhibited by KSR-directed inhibitors. This finding has implications in signaling and the design of scaffold protein-aimed therapeutics.
Review
Medicine, General & Internal
Cameron D. Haydinger, Lisia Barros Ferreira, Keryn A. Williams, Justine R. Smith
Summary: Macular edema is the accumulation of fluid in the central retina, which is a complication of various retinal diseases. It can lead to significant visual impairment and blindness. The dysregulation of the blood-retinal barrier and the increase in osmotic pressure are the main causes of macular edema. Current treatments focus on blocking vasoactive and inflammatory mediators. This review provides a clinical overview, discusses the mechanisms of the disease and current treatments, and identifies areas for future research.
FRONTIERS IN MEDICINE
(2023)
Review
Biology
Cameron D. Haydinger, Liam M. Ashander, Alwin Chun Rong Tan, Justine R. Smith
Summary: Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein that plays important roles in the immune system and is involved in various diseases. It mediates cellular adhesive interactions and is upregulated in inflammation. This review provides a comprehensive summary of the structure and regulation of ICAM1 gene and the ICAM-1 protein, discusses its functions in the immune system and diseases, and explores current therapeutics and future advancements.
Article
Oncology
Aoife Nolan, Cinzia Raso, Walter Kolch, Alex von Kriegsheim, Kieran Wynne, David Matallanas
Summary: RAS proteins play a crucial role in cell signalling, regulating cell functions such as proliferation, differentiation, and death. Mutations in genes of this family, particularly KRAS, are common and were believed to constitutively activate KRAS. However, recent findings show that some mutants can switch between active and inactive states. This, along with the development of covalent KRASG12C inhibitors, has led to the emergence of KRAS inhibitors in clinical use. Despite this, resistance to targeted therapies remains a challenge, and effective treatments for other KRAS mutants are lacking. To overcome these hurdles and accelerate RAS targeting therapies, a comprehensive understanding of the molecular mechanisms underlying KRAS signalling networks and the differences in downstream signalling of KRAS mutants is needed. This study employed affinity purification mass-spectrometry proteomics to analyze the interactome of KRAS wild-type and three KRAS mutants. Through bioinformatic analysis and experimental validation, the researchers mapped the signalling network mediated by different KRAS proteins. The study also revealed novel crosstalk between KRAS and effector pathways, including AKT and JAK-STAT signalling modules.
Article
Endocrinology & Metabolism
Shuijie Li, Wenyu Li, Juan Yuan, Petra Bullova, Jieyu Wu, Xuepei Zhang, Yong Liu, Monika Plescher, Javier Rodriguez, Oscar C. Bedoya-Reina, Paulo R. Jannig, Paula Valente-Silva, Meng Yu, Marie Arsenian Henriksson, Roman A. Zubarev, Anna Smed-Sorensen, Carolyn K. Suzuki, Jorge L. Ruas, Johan Holmberg, Catharina Larsson, C. Christofer Juhlin, Alex von Kriegsheim, Yihai Cao, Susanne Schlisio
Summary: This study reveals the oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, and its connection to tumorigenesis in von Hippel-Lindau syndrome. The findings suggest that impaired mitochondrial biogenesis is linked to VHL tumorigenesis, and targeting mitochondria could sensitize therapy-resistant VHL tumors.
Article
Medicine, Research & Experimental
Angela M. Araujo, Andrea Abaurrea, Peio Azcoaga, Joanna Lopez-Velazco, Sara Manzano, Javier Rodriguez, Ricardo Rezola, Leire Egia-Mendikute, Fatima Valdes-Mora, Juana M. Flores, Liam Jenkins, Laura Pulido, Inaki Osorio-Querejeta, Patricia Fernandez-Nogueira, Nicola Ferrari, Cristina Viera, Natalia Martin-Martin, Alexandar Tzankov, Serenella Eppenberger-Castori, Isabel Alvarez-Lopez, Ander Urruticoechea, Paloma Bragado, Nicholas Coleman, Asis Palazon, Arkaitz Carracedo, David Gallego-Ortega, Fernando Calvo, Clare M. Isacke, Maria M. Caffarel, Charles H. Lawrie
Summary: This study reveals the pivotal role of the cytokine oncostatin M (OSM) in regulating interactions between immune and nonimmune stromal cells and epithelial cancer cells. It demonstrates that the stromal OSM/OSMR axis reprograms the tumor microenvironment and plays a key role in breast cancer progression.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Christopher Mapperley, Louie N. van de Lagemaat, Hannah Lawson, Andrea Tavosanis, Jasmin Paris, Joana Campos, David Wotherspoon, Jozef Durko, Annika Sarapuu, Junho Choe, Ivayla Ivanova, Daniela S. Krause, Alex von Kriegsheim, Christian Much, Marcos Morgan, Richard I. Gregory, Adam J. Mead, Donal O'Carroll, Kamil R. Kranc
Summary: The study reveals that YTHDF2 acts as a repressor of inflammatory pathways in hematopoietic stem cells, and long-term deletion of YTHDF2 results in HSC dysfunction and ultimately leads to multilineage hematopoiesis failure.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
