Review
Oncology
Naoe Taira Nihira, Yoshio Miki
Summary: This article discusses the mechanisms by which tumor cells acquire immune tolerance through inhibiting T-cell activation and function, as well as the successes and limitations of immunotherapy targeting immune checkpoint molecules. The article highlights the importance of post-translational modifications in modulating the function of inhibitory immune checkpoint molecules.
FRONTIERS IN ONCOLOGY
(2022)
Review
Immunology
Chong Feng, Lening Zhang, Xin Chang, Dongliang Qin, Tao Zhang
Summary: The immune checkpoint molecules PD-1 and PD-L1 are promising targets for tumor immunotherapy. PD-L1 overexpression on tumor cells inhibits T cell activation by binding to PD-1, leading to tumor immune escape. Targeting PD-1/PD-L1 involves blocking this binding and restoring immune cell killing effect.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
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
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
Oncology
Xiaoming Dai, Yang Gao, Wenyi Wei
Summary: Antibody therapies targeting PD-1/PD-L1 have revolutionized cancer treatment, but only a small fraction of patients respond well. Understanding the molecular mechanisms regulating PD-1/PD-L1 expression can lead to improvements in anti-PD-1/PD-L1 therapy.
SEMINARS IN CANCER BIOLOGY
(2022)
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
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.
Review
Immunology
Yanqing Li, Runfang Zhang, Hu Hei
Summary: Protein post-translational modification (PTM) is a regulatory mechanism that involves adding or removing specific chemical groups on amino acid residues to modulate protein activity, localization, expression, and interactions. It plays a vital role in important biological processes and the occurrence and development of diseases, as well as in tumor immunotherapy. This review comprehensively summarizes the role of several types of PTMs in tumor immunotherapy and provides new insights and future research directions.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
Review
Biochemistry & Molecular Biology
Min-Seon Hwang, Jingyeong Park, Yunha Ham, In Hye Lee, Kyung-Hee Chun
Summary: Adipocyte senescence, caused by factors like DNA damage, oxidative stress, telomere dysfunction, and chronic lipid accumulation, can disrupt metabolic homeostasis and lead to various diseases and aging. Understanding the role of post-translational modifications (PTMs) in the regulation of adipocyte senescence is crucial for developing effective strategies to combat metabolic diseases.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
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)
Review
Biochemistry & Molecular Biology
Jing Xia, Songhong Jiang, Shiqi Dong, Yonghong Liao, Yang Zhou
Summary: Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) activate the NLRP3 inflammasome, leading to the production of active caspase-1, interleukin-1 beta (IL-1 beta), and gasdermin D (GSDMD), resulting in pyroptosis and inflammation. Dysregulated NLRP3 inflammasome activation is implicated in various diseases, making it a potential target for disease prevention and treatment. Recent studies have demonstrated that post-translational modifications (PTMs) play a crucial role in regulating NLRP3 inflammasome activity. This review focuses on PTMs of NLRP3 inflammasome components and their impact on its activity regulation, providing insights into the mechanisms underlying NLRP3 inflammasome activation and control.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Sony Shrestha, Amuza Byaruhanga Lucky, Awtum Marie Brashear, Xiaolian Li, Liwang Cui, Jun Miao
Summary: This study profiled the histone post-translational modifications (PTMs) in the development of Plasmodium falciparum gametocytes, revealing novel PTM sites and distinct patterns from asexual stages. The results suggest that these PTMs play critical roles in gametocyte development and provide insights into the epigenetic regulation in the life cycle of the malaria parasite.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Neurosciences
Martina Stazi, Oliver Wirths
Summary: The study demonstrates that chronic treatment with memantine has positive effects on an Alzheimer's disease mouse model, such as reducing neuron loss and improving cognitive function.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Behavioral Sciences
Martina Stazi, Oliver Wirths
Summary: The research demonstrates that prolonged physical activity and cognitive stimulation in a mouse model of AD overexpressing only Aβ(4-42) peptides lead to preservation of recognition and spatial memory, rescue of motor deficits, and improvement of phenotypes in the Morris water maze task. These findings support the notion that physical activity and cognitive stimulation could be effective strategies in preventing age-related neurodegenerative disorders like AD.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Silvia Zampar, Oliver Wirths
Summary: The relationship between extracellular amyloid-beta deposits and intracellular accumulation of hyperphosphorylated tau in Alzheimer's Disease (AD) remains not fully understood. Studies have shown that A beta deposits trigger tau phosphorylation and accumulation, but the impact of different A beta variants on tau pathology is still debated. Crossbreeding studies on transgenic mouse models suggest that A beta(4-42) peptides may have partial negative effects on motor performance and spatial memory in aged mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Freyja Aichholzer, Hans-Wolfgang Klafki, Isabella Ogorek, Jonathan Vogelgsang, Jens Wiltfang, Norbert Scherbaum, Sascha Weggen, Oliver Wirths
Summary: Despite the correlation between CSF GPNMB levels and other parameters such as aging and CSF pTau levels, the study results indicate that GPNMB levels in CSF cannot distinguish between AD or other neurological diseases. The findings do not support GPNMB as a valuable neurochemical diagnostic biomarker of AD, suggesting the need for further studies involving healthy control individuals.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Martina Stazi, Sandra Lehmann, M. Sadman Sakib, Tonatiuh Pena-Centeno, Luca Buschgens, Andre Fischer, Sascha Weggen, Oliver Wirths
Summary: Research suggests that moderate caffeine consumption reduces the risk of Alzheimer's disease and can improve neuronal loss, behavioral deficits, and neurogenesis in mouse models of the disease. The study challenges the belief that caffeine is anti-amyloidogenic and highlights the potential role of promoting neurogenesis in its beneficial effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Priyanka Rajeev Menon, Julia Staab, Anke Gregus, Oliver Wirths, Thomas Meyer
Summary: U-STAT1 affects the signal transduction mediated by P-STAT1 and alters the nucleo-cytoplasmic distribution of P-STAT1. U-STAT1 maintains high levels of cytoplasmic STAT1 by inhibiting the nuclear accumulation of P-STAT1, while preserving IFN γ-induced gene expression.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Liana Marengo, Fred Armbrust, Caroline Schoenherr, Steffen E. Storck, Ulrich Schmitt, Silvia Zampar, Oliver Wirths, Hermann Altmeppen, Markus Glatzel, Christoph Kaether, Sascha Weggen, Christoph Becker-Pauly, Claus U. Pietrzik
Summary: This study reports the generation of a transgenic mouse model of AD lacking the functional Mep1b gene (APP/lon x Mep1b(-/-)). The results showed that when meprin beta is absent, the levels of A beta 1-40 and 1-42 are reduced in APP/lon mice, and the deposition of N-terminally truncated A beta 2-x peptide is also decreased. Importantly, the loss of meprin beta improved cognitive abilities in APP/lon mice.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Clinical Neurology
Martina Stazi, Silvia Zampar, Madeleine Nadolny, Luca Buschgens, Thomas Meyer, Oliver Wirths
Summary: This study found that caffeine supplementation combined with enriched environment can enhance memory function and may have a preventive effect on age-related cognitive decline.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2022)
Article
Cell Biology
Lena Sophie Behrendsen, Priyanka Rajeev Menon, Muhammad Jawad Khan, Anke Gregus, Oliver Wirths, Thomas Meyer, Julia Staab
Summary: Although previously reported as an activating mutation, the STAT3-D427H mutant does not display increased cytokine-induced tyrosine phosphorylation or altered nuclear accumulation compared to the WT protein. However, the D427H mutant shows enhanced binding to STAT-specific DNA-binding sites but with reduced sequence specificity and dissociation rate from DNA.
BMC MOLECULAR AND CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Martina Stazi, Silvia Zampar, Hans-Wolfgang Klafki, Thomas Meyer, Oliver Wirths
Summary: A range of factors, including physical activity and caffeine supplementation, may reduce the risk of developing dementia and Alzheimer's disease in later life. Previous studies have shown that chronic oral caffeine supplementation and enriched environment housing can improve memory and cognitive performance in AD mice. However, combining physical activity and caffeine did not have a major additive effect in improving learning and memory function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Thomas Liepold, Hans-Wolfgang Klafki, Sathish Kumar, Jochen Walter, Oliver Wirths, Jens Wiltfang, Olaf Jahn
Summary: Amyloid-fi (Afi) peptides, including modified variants, are believed to be involved in Alzheimer's disease. However, previous studies relied on antibody-based approaches, and further analyses are needed to verify the existence of phosphorylated Afi species in brain samples using mass spectrometry. A customized matrix formulation called TOPAC was developed to improve the detection of synthetic phosphorylated Afi species. TOPAC showed higher signal intensities and minimal oxidation and loss for intact and proteolytic cleavage products, making it a valuable tool for detecting and characterizing phosphorylated Afi species in biological samples.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Neurosciences
Hans-Wolfgang Klafki, Barbara Morgado, Oliver Wirths, Olaf Jahn, Chris Bauer, Hermann Esselmann, Johannes Schuchhardt, Jens Wiltfang
Summary: Our findings suggest that the relatively small difference in the plasma A beta 42/40 ratio between subjects with and without evidence of brain amyloidosis can be accentuated by specifically measuring A beta 1-42/1-40 instead of A beta X-42/X-40.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Multidisciplinary Sciences
Constanze Depp, Ting Sun, Andrew Octavian Sasmita, Lena Spieth, Stefan A. Berghoff, Taisiia Nazarenko, Katharina Overhoff, Agnes A. Steixner-Kumar, Swati Subramanian, Sahab Arinrad, Torben Ruhwedel, Wiebke Moebius, Sandra Goebbels, Gesine Saher, Hauke B. Werner, Alkmini Damkou, Silvia Zampar, Oliver Wirths, Maik Thalmann, Mikael Simons, Takashi Saito, Takaomi Saido, Dilja Krueger-Burg, Riki Kawaguchi, Michael Willem, Christian Haass, Daniel Geschwind, Hannelore Ehrenreich, Ruth Stassart, Klaus-Armin Nave
Summary: The main risk factor for Alzheimer's disease (AD), the leading cause of dementia, is age, but the reasons for this are still poorly understood. In this study, researchers found that age-related structural defects of myelin lead to the formation of amyloid-beta (Aβ) plaques, a hallmark of AD. Improving the health of oligodendrocytes and the integrity of myelin could be a promising target for delaying and slowing the progression of AD.
Article
Cardiac & Cardiovascular Systems
Asmma Doudin, Theresa Riebeling, Julia Staab, Priyanka Rajeev Menon, Fred Luehder, Oliver Wirths, Uwe Vinkemeier, Aleksandar Ivetic, Thomas Meyer
Summary: This study explored the functional significance of co-operative DNA binding of STAT1 in an experimental murine model of acute myocardial infarction (MI). The results showed that a loss of STAT1 tetramer stabilization improved survival and left ventricular dysfunction in male and female mice, respectively. Additionally, dysfunctional STAT1 signaling caused a compensatory increase in STAT3 expression and promoted early infiltration of immune cells in the infarcted area.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cell Biology
Linus Remling, Anke Gregus, Oliver Wirths, Thomas Meyer, Julia Staab
Summary: In this study, we have identified a previously unknown interdimeric interaction site involved in the termination of STAT1 signaling. The introduction of a glutamic acid-to-alanine mutation at position 169 in the coiled-coil domain (CCD) resulted in increased tyrosine phosphorylation, accelerated nuclear import, enhanced DNA-binding affinity, and transcriptional activity compared to the wild-type protein. Furthermore, we demonstrated that the E169 residue in the CCD mediates the release of the dimer from DNA in an autoinhibitory manner.
CELL COMMUNICATION AND SIGNALING
(2023)