Article
Developmental Biology
Casey Ah-Cann, Verena C. Wimmer, Clare E. Weeden, Claire Marceaux, Charity W. Law, Laura Galvis, Caitlin E. Filby, Joy Liu, Kelsey Breslin, Tracy Willson, Matthew E. Ritchie, Marnie E. Blewitt, Marie-Liesse Asselin-Labat
Summary: The development of a branching tree in the embryonic lung is crucial for a fully mature functional lung at birth, with Sox9(+) cells playing a key role in this process. This study identified aurora kinase b (Aurkb) as an essential regulator of Sox9(+) cells, with its loss leading to insufficient branch development. The research demonstrates the potential of genetic screens in identifying regulators of lung development.
Review
Medicine, Research & Experimental
Pengfei Ji, Guokun Zhang, Yanan Guo, Haoyun Song, Xinyi Yuan, Xiaohui Hu, Zhao Guo, Peng Xia, Rong Shen, Degui Wang
Summary: DNA damage leads to increased genomic instability and various diseases. Post-translational modifications, including crotonylation, play significant roles in maintaining genomic stability and regulating biological processes and disease development.
Article
Cell Biology
Yu Chen, Jie Sun, Zhenyu Ju, Zhao-Qi Wang, Tangliang Li
Summary: This study reveals the essential role of the DNA double-strand repair molecule Nbs1 in embryonic HSC development and hematopoiesis. Nbs1 deficiency leads to persistent DNA breaks in embryonic HSCs, affecting their development and causing perinatal lethality in mice. Additionally, the discrepancies in response to DNA damages between Nbs1 null HSCs and hematopoietic progenitors may be mediated by different levels of p53 signaling.
CELL PROLIFERATION
(2021)
Article
Cell & Tissue Engineering
Lei Wang, Xiaojun Tan, Lu Chen, Sisi Xu, Weiping Huang, Nan Chen, Yizhou Wu, Chunyan Wang, Daqiang Zhou, Mangmang Li
Summary: Research findings show that Sall4 negatively regulates DNA damage-induced apoptosis in mESCs by mediating p53 recognition of repressed target genes. Sall4 depletion compromises p53-mediated repression and promotes activation of pro-apoptotic genes.
Article
Cell & Tissue Engineering
Richa Basundra, Sahil Kapoor, Emilie Hollville, Nazanin Kiapour, Adriana Beltran Lopez, Nicole Marie Melchiorre, Mohanish Deshmukh
Summary: NOXA plays a crucial role in hES cells by effectively antagonizing MCL1 to facilitate rapid apoptosis.
Article
Biochemistry & Molecular Biology
Michael D. Rushton, Emily A. Saunderson, Hemalvi Patani, Michael R. Green, Gabriella Ficz
Summary: The propagation of DNA methylation during cell division relies on the recognition of methylated cytosines by UHRF1. In a study on reprogramming mouse embryonic stem cells, it was found that despite high levels of Uhrf1 transcript, the protein was targeted for degradation, resulting in loss of DNA methylation. The study also identified key enzymes in glucose metabolism, nucleotide metabolism, and the Pi3K/AKT/mTOR pathway as candidates that converge upon UHRF1 and control its degradation.
Review
Cell Biology
Isadora Carolina Betim Pavan, Andressa Peres de Oliveira, Pedro Rafael Firmino Dias, Fernanda Luisa Basei, Luidy Kazuo Issayama, Camila de Castro Ferezin, Fernando Riback Silva, Ana Luisa Rodrigues de Oliveira, Livia Alves dos Reis Moura, Mariana Bonjiorno Martins, Fernando Moreira Simabuco, Joerg Kobarg
Summary: NEKs are a family of Ser/Thr protein kinases that play important roles in cell cycle, mitosis, DNA damage response, and other biological functions in vertebrate cells. Research has primarily focused on their involvement in mitosis regulation and cell cycle, but recent studies have also shown their participation in DNA damage response pathways.
Article
Multidisciplinary Sciences
Luke A. Yates, Elias A. Tannous, R. Marc Morgan, Peter M. Burgers, Xiaodong Zhang
Summary: This study reveals the phosphorylation circuit that regulates checkpoint recruitment and function in response to DNA damage. The interaction between Ddc2 and RPA modulates the association between RPA and ssDNA, and phosphorylated Ddc2 enhances its recruitment to RPA-ssDNA, promoting DNA damage checkpoint signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Paula Mondragon, Sungmin Hwang, Lakshmi Kasirajan, Rebecca Oyetoro, Angelina Nasthas, Emily Winters, Ricardo L. Couto-Rodriguez, Amy Schmid, Julie A. Maupin-Furlow
Summary: This study identifies a TrmB-like protein (OxsR) that functions as a thiol-based transcriptional regulator in response to oxidative stress, particularly hypochlorite stress. OxsR binds to specific regions of DNA during hypochlorite stress, which are proximal to oxidative stress operons. Further analysis reveals that OxsR acts as both a transcriptional activator and repressor during hypochlorite stress. The presence of a conserved cysteine residue and a CG-rich motif in the promoter region suggests a widespread redox signaling mechanism in archaea.
Article
Biochemistry & Molecular Biology
Dan Li, Jihong Yang, Vikas Malik, Yuting Huang, Xin Huang, Hongwei Zhou, Jianlong Wang
Summary: RNA helicase eIF4A3 plays a crucial role in maintaining pluripotency of stem cells by post-transcriptionally controlling the cell cycle, particularly the efficient nuclear export of Ccnb1 mRNA.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Aleksandra Kozyczkowska, Sebastian R. Najle, Eduard Ocana-Pallares, Cristina Areste, Victoria Shabardina, Patricia S. Ara, Inaki Ruiz-Trillo, Elena Casacuberta
Summary: Recent research on the genomes of unicellular relatives of animals has improved our understanding of genetic changes during animal evolution, but specific cellular modifications remain unclear. A study found that a corallochytrean displays a non-linear life cycle, being binucleate for most of its life cycle.
Review
Cell Biology
Davide Cinat, Robert P. Coppes, Lara Barazzuol
Summary: This review discusses how DNA damage affects the maintenance and function of stem cells in adult tissues and neoplasms, leading to inflammatory responses and changes in the microenvironment. DNA damage can induce cell senescence, increase pro-inflammatory factors release, and modulate immune responses, potentially impacting tissue homeostasis and cancer development. Understanding the DNA damage-induced immunomodulatory responses on stem cell microenvironment may provide insights into age-related diseases and cancer, offering novel treatment strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Evan K. Day, Qing Zhong, Benjamin Purow, Matthew J. Lazzara
Summary: In glioblastoma, the inhibition of SHP2 has diverse and context-dependent effects on signaling pathways, which may make them useful components of some combination therapies but not others.
Article
Cell Biology
Fang Cao, Yunpeng Jiang, Lin Chang, Hongzhen Du, De Chang, Chunxiao Pan, Xiaozheng Huang, Donglin Yu, Mi Zhang, Yongna Fan, Xiaocui Bian, Kailong Li
Summary: Pancreatic cancer is characterized by early metastasis and limited response to current therapies. Through a genetic screening platform, YWHAZ has been identified as a key regulator of pancreatic cancer metastasis. Overexpression of YWHAZ promotes cell migration and invasion, and is associated with poor prognosis in pancreatic cancer patients.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Md Akram Hossain, Yunfeng Lin, Garrett Driscoll, Jia Li, Anne McMahon, Joshua Matos, Haichao Zhao, Daisuke Tsuchimoto, Yusaku Nakabeppu, Jianjun Zhao, Shan Yan
Summary: APE2 is essential for activating the ATR DDR pathway in response to various stressful conditions in Xenopus laevis egg extracts and human pancreatic cancer cells. Inhibition of APE2 leads to increased DNA damage and sensitizes cancer cells to chemotherapy drugs, indicating its crucial role in maintaining genome integrity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pathology
Lise M. van Wijk, Andreea B. Nilas, Harry Vrieling, Maaike P. G. Vreeswijk
Summary: This review provides an overview of currently available HRD tests and discusses their pros and cons, sensitivity for HRD tumor identification, concordance with other HRD tests, and ability to predict therapy response. With the increasing use of PARPi in cancer treatment, there is an urgent need to incorporate HRD testing into routine clinical practice.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2022)
Article
Biology
Zilu Ye, Tanveer S. Batth, Patrick Ruether, Jesper Olsen
Summary: This study investigates the effects of carrier proteomes on single cell proteomics. The results show that high levels of carrier proteomes limit quantitative precision and signal intensity, leading to limited identification of regulated proteins.
COMMUNICATIONS BIOLOGY
(2022)
Review
Genetics & Heredity
Ana Martinez-Val, Ulises H. Guzman, Jesper Olsen
Summary: Proteins are essential for transmitting encoded genetic information, and proteomics aims to understand their molecular functions in a biological context. Mass spectrometry-based proteomics is the preferred technology for studying proteomes, contributing to biomarker discovery and fundamental molecular biology. This review outlines how mass spectrometry technology has evolved to study the human proteome and its posttranslational modifications in depth, and discusses the potential of single-cell resolution proteomics.
ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Zi Wang, Bircan Coban, Chen-Yi Liao, Yao-Jun Chen, Qiuyu Liu, Erik H. J. Danen
Summary: GRHL2 has different roles in different breast cancer subtypes, promoting cancer growth in some subtypes and suppressing cancer progression in others. Its expression is increased in all subtypes of breast cancer and inversely correlated with overall survival in basal-like breast cancer patients. GRHL2 regulates cell-cell junction, epithelial migration, and proliferation in both luminal and basal A breast cancer subtypes, but has distinct effects on cell cycle arrest and migration in these subtypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Anders H. Kverneland, Ole Ostergaard, Kristina Bennet Emdal, Inge Marie Svane, Jesper Velgaard Olsen
Summary: This study demonstrates that enrichment of extracellular vesicles (EVs) by ultracentrifugation can significantly increase the depth of the plasma proteome analysis. By optimizing the workflow, over two thousand proteins can be quantified in a short time using label-free quantification and data independent acquisition (DIA), enabling high-throughput analysis of plasma samples and supporting potential biomarker discovery in the future.
Review
Immunology
Giulia Franciosa, Anders H. Kverneland, Agnete W. P. Jensen, Marco Donia, Jesper V. Olsen
Summary: Cancer survival relies on tumor cells evading immune recognition, but immunotherapy has shown promising results in metastatic cancers. Resistance mechanisms limit efficacy, so understanding the interplay between immune cells and tumors is crucial. Mass spectrometry-based proteomics may provide insights into tumor immunity and cancer immunotherapies, allowing for translational and clinical discoveries.
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Article
Oncology
Alessandro Gregori, Cecilia Bergonzini, Mjriam Capula, Giulia Mantini, Fatemeh Khojasteh-Leylakoohi, Annalisa Comandatore, Ghazaleh Khalili-Tanha, Alireza Khooei, Luca Morelli, Amir Avan, Erik H. Danen, Thomas Schmidt, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemoresistant cancer, with a stiff stroma surrounding it playing a role in chemoresistance. High expression of the mechanical sensor ITGA2 correlated with a poor prognosis in PDAC patients, and increased matrix stiffness led to the expression of ITGA2 and chemoresistance to gemcitabine. ITGA2 could be a potential therapeutic target to overcome gemcitabine resistance.
Article
Cell Biology
Chanchal Chauhan, Ana Martinez-Val, Rainer Niedenthal, Jesper Velgaard Olsen, Alexey Kotlyarov, Simon Bekker-Jensen, Matthias Gaestel, Manoj B. Menon
Summary: The TNF receptor-interacting protein kinases (RIPK)-1 and 3 regulate cell death response pathways. RIPK1 determines cell survival or death by associating with distinct complexes, while RIPK3 is a target of PRMT5-mediated arginine dimethylation. This study uncovers PRMT5-mediated RIPK3 methylation as a novel modulator of RIPK1-dependent signaling.
CELL DEATH DISCOVERY
(2023)
Article
Chemistry, Analytical
Teeradon Phlairaharn, Zilu Ye, Elena Krismer, Anna-Kathrine Pedersen, Maik Pietzner, Jesper V. Olsen, Erwin M. Schoof, Brian C. Searle
Summary: A linear ion trap (LIT) is a cost-effective and robust mass spectrometer with fast scanning speed and high sensitivity. Its primary disadvantage is inferior mass accuracy compared to more commonly used time-of-flight or orbitrap (OT) mass analyzers. In this study, we demonstrate the potential versatility of the LIT as a stand-alone mass analyzer for low-input proteomics, including library generation. We optimized LIT data acquisition methods, performed library-free searches, and successfully generated matrix-matched calibration curves using only 10 ng of starting material.
ANALYTICAL CHEMISTRY
(2023)
Article
Oncology
Qiuyu Liu, Nasi Liu, Vera van der Noord, Wanda van der Stel, Bob van de Water, Erik H. J. Danen, Sylvia E. Le Devedec
Summary: Hypoxia is associated with disease progression and poor prognosis in breast cancer, but little is known about the response of different breast cancer subtypes to hypoxia. This study compared the response of luminal and basal A subtype cell lines to acute and chronic hypoxia. The results showed that both subtypes activate HIF-related pathways, but basal A cells are less affected by hypoxia compared to luminal cells. Notably, hypoxia-induced gene networks were associated with worse survival in breast cancer patients. Different adaptation programs were observed in these subtypes, indicating their contribution to the progression of breast cancer.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Review
Biochemistry & Molecular Biology
Giulia Franciosa, Marie Locard-Paulet, Lars J. Jensen, Jesper Olsen
Summary: Mass spectrometry-based phosphoproteomics is the leading method for studying global kinase signaling. Various technological improvements and bioinformatic resources are available to accurately identify and quantify phosphopeptides, interpret large-scale data, and understand kinase network functional role. This review presents the latest experimental and bioinformatic tools for profiling protein kinase signaling networks and their applications in biomedicine.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Cell Biology
V. Nieddu, V. Melocchi, C. Battistini, G. Franciosa, M. Lupia, C. Stellato, G. Bertalot, J. V. Olsen, N. Colombo, F. Bianchi, U. Cavallaro
Summary: Ovarian cancer (OC) has the highest mortality rate among gynecological tumors, primarily due to early peritoneal dissemination, tumor relapse, and chemoresistance. These events are initiated and sustained by ovarian cancer stem cells (OCSC) with self-renewing and tumor-initiating properties. Interfering with OCSC function could offer novel therapeutic perspectives.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Fabiana Di Gianvincenzo, Cecil Krarup Andersen, Troels Filtenborg, Meaghan Mackie, Madeleine Ernst, Jazmin Ramos Madrigal, Jesper V. Olsen, Jorge Wadum, Enrico Cappellini
Summary: The application of mass spectrometry-based proteomics to artworks is valuable for characterizing protein-based materials and reconstructing the artwork's history. Proteomic analysis of Danish Golden Age canvas paintings identified cereal and yeast proteins, indicating the use of a beer brewing by-product as a binder, consistent with local artists' manuals. Metabolomic analysis supports these findings and suggests the use of drying oils. This study highlights the value of untargeted proteomics in correlating unconventional artistic materials with local culture.
Article
Multidisciplinary Sciences
Tanveer S. Batth, Jonas L. Simonsen, Cristina Hernandez-Rollan, Soren Brander, Jens Preben Morth, Katja S. Johansen, Morten H. H. Norholm, Jakob B. Hoof, Jesper V. Olsen
Summary: The methyltransferase NHMT responsible for N-terminal histidine methylation modification is identified and validated through mass spectrometry-based proteomics and CRISPR/Cas9. NHMT protects LPMOs from auto-oxidative inactivation by methylating the His1 site. The biotechnological potential of recombinant production of proteins and peptides with this specific post-translational modification is demonstrated.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Ulises H. H. Guzman, Henriette Aksnes, Rasmus Ree, Nicolai Krogh, Magnus E. E. Jakobsson, Lars J. J. Jensen, Thomas Arnesen, Jesper V. V. Olsen
Summary: Protein N-terminal (Nt) acetylation is a common modification in eukaryotes and plays a crucial role in promoting stability of the proteome. However, the functional impact of Nt-acetylation has been hindered by its pleiotropic effects. In this study, we used proteomics approaches to analyze the effects of NatA deficiency in Saccharomyces cerevisiae and found that it leads to global proteome remodeling and decreased thermostability of ribosomes.
NATURE COMMUNICATIONS
(2023)