Article
Biochemistry & Molecular Biology
Nicholas K. K. Tonks
Summary: In October 2020, a celebration for Eddy Fischer's 100th birthday was held via ZOOM due to COVID restrictions. Eddy Fischer, along with Ed Krebs, made significant contributions to the field of signal transduction through their discovery of reversible protein phosphorylation. This work has had a profound impact on the biotechnology industry and the treatment of various cancers.
Review
Immunology
Frederic Bornancin, Carien Dekker
Summary: This review focuses on the regulation of the NLRP3 inflammasome by phosphorylation and dephosphorylation, and discusses the kinases and phosphatases that have been reported to modulate NLRP3 activity. The aim is to integrate the current understanding and highlight potential gaps for further studies.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Funda M. Kar, Andreas Hochwagen
Summary: Germ cells rely on a complex network of surveillance mechanisms to ensure the production of euploid gametes during meiosis. Dynamic protein phosphorylation, controlled by kinases and phosphatases, plays a crucial role in regulating chromosomal and cellular behavior throughout meiotic prophase. This review discusses common principles and detailed examples of how phosphorylation events are utilized to ensure faithful passage of chromosomes from one generation to the next.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Emily C. Suter, Eva M. Schmid, Andrew R. Harris, Erik Voets, Brian Francica, Daniel A. Fletcher
Summary: The study reveals that the phagocytic decisions of macrophages are regulated by the ratio of activating ligand to inhibitory ligand, and a ratio of at least 10:1 is required for promoting phagocytosis. Ratiometric signaling is crucial for phagocytosis of tumor cells and can be modified by blocking SIRP alpha.
Article
Multidisciplinary Sciences
Aashirwad Shahi, Jacob Kahle, Chandler Hopkins, Maria Diakonova
Summary: This study elucidates the diverse functions of JAK2 in cells, including involvement in cell proliferation, cell cycle regulation, and centrosome amplification. The SH2 domain and kinase activity play crucial roles in the centrosome localization of JAK2 and regulation of cell growth.
Article
Oncology
Marie Schwarz, Sophie Rizzo, Walter Espinoza Paz, Anne Kresinsky, Damien Thevenin, Joerg P. Mueller
Summary: This study demonstrates that mutations in PTPRJ can increase its activity and impair FLT3 activity in acute myeloid leukemia cells, thereby restricting the transformation and proliferation abilities of leukemic cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
John Lee, Rongbing Chen, T. Mohanakumar, Ross Bremner, Sumeet Mittal, Timothy P. Fleming
Summary: The study identified activated EGFR, ErbB2, and ErbB3 receptors in esophageal cancer cells, and found that treatment with the pan-EGFR family inhibitor afatinib could inhibit tumor cell proliferation and growth in both in vitro and animal xenograft models. Targeting activated TKRs may serve as a personalized treatment strategy for EC tumors.
ONCOTARGETS AND THERAPY
(2021)
Article
Biology
Mohammad Arefian, N. Bhagya, T. S. Keshava Prasad
Summary: Protein phosphorylation plays a critical role in regulating plant growth, especially during the morphogenesis at flowering stage. Further research on the phosphorylation regulation mechanisms during flowering is needed, which may have a positive impact on increasing crop productivity.
BIOLOGICAL REVIEWS
(2021)
Article
Oncology
Baoxue Duan, Changying Wang, Zeng Liu, Xiaoyu Yang
Summary: This study demonstrated that the overexpression of USP8 in melanoma is associated with increased cell activities and resistance to therapeutic drugs. Inhibition of USP8 activity can lead to reduced expression of multiple oncogenic RTKs and disruption of downstream survival signaling pathways, promoting apoptosis in melanoma cells. This suggests that USP8 may be a potential target for sensitizing melanoma cells to therapy.
CANCER MANAGEMENT AND RESEARCH
(2021)
Article
Oncology
Henriette U. Balinda, Alanna Sedgwick, Crislyn D'Souza-Schorey
Summary: MLK3 plays a critical role in regulating melanoma cell invasion, and loss of MLK3 leads to hyperactivation of ERK, promoting melanoma invasion.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Evangelia Papadimitriou, Vasiliki K. Kanellopoulou
Summary: Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is highly expressed during embryonic development but limited in adulthood. It plays a role in oligodendrocytes' survival and maturation in the central nervous system. In gliomas, PTPRZ1 is significantly upregulated and studied as a potential cancer driver and therapy target. However, its functional significance and tumor-suppressor role in other cancer types need further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yaroslav Kolesnikov, Serhii Kretynin, Yaroslava Bukhonska, Igor Pokotylo, Eric Ruelland, Jan Martinec, Volodymyr Kravets
Summary: Cells sense extracellular signals and regulate their metabolism and physiology accordingly. The plasma membrane plays a crucial role in this process by acting as an informational barrier and responding to regulatory inputs. Phosphatidic acid (PA) is a well-known intracellular messenger that regulates various cellular processes and is involved in plant growth, development, and stress tolerance. This review focuses on the primary signaling events triggered by rapid PA accumulation in plant cells, and discusses its role in mediating the response to hormones and hormone-like regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
David E. Heppner
Summary: The activity of SFKs kinases is regulated by protein phosphorylation, and the oxidation state of their redox-active cysteine residues is influenced by the local structural environment. Conserved and non-conserved cysteine residues exhibit differences in oxidation activity and structural environments.
Article
Biochemistry & Molecular Biology
Qiujiao Yang, Jianhang Guo, Hairuo Zeng, Lahong Xu, Jiao Xue, Shi Xiao, Jian-Feng Li
Summary: CDG1 functions as a negative regulator in Arabidopsis, negatively regulating flg22- and chitin-triggered immunity by promoting FLS2 and CERK1 degradation. Additionally, CDG1 is partially required for AvrRpm1-induced RIN4 phosphorylation.
Review
Medicine, General & Internal
Steven Didik, Hao Wang, Adewale Segun James, Lily Slotabec, Ji Li
Summary: Hypertension is a complex condition affecting millions of individuals globally, with its prevalence projected to increase. This review explores the development of hypertension and highlights the potential of using the antioxidative protein Sestrin2 (Sesn2) as a therapeutic target. The review also discusses the various sources of increased reactive oxygen species (ROS) in hypertension and presents the structural and functional characteristics of Sesn2.
Article
Oncology
S. Peters, J-L Pujol, U. Dafni, M. Domine, S. Popat, M. Reck, J. Andrade, A. Becker, D. Moro-Sibilot, A. Curioni-Fontecedro, O. Molinier, K. Nackaerts, A. Insa Molla, R. Gervais, G. Lopez Vivanco, J. Madelaine, J. Mazieres, M. Faehling, F. Griesinger, M. Majem, J. L. Gonzalez Larriba, M. Provencio Pulla, K. Vervita, H. Roschitzki-Voser, B. Ruepp, P. Mitchell, R. A. Stahel, C. Le Pechoux, D. De Ruysscher
Summary: The STIMULI trial did not demonstrate improvement in PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in limited-disease small-cell lung cancer. The higher rates of grade >= 3 adverse events and treatment discontinuation in the experimental arm may have influenced the efficacy results.
ANNALS OF ONCOLOGY
(2022)
Article
Respiratory System
Arutha Kulasinghe, Chin Wee Tan, Anna Flavia Ribeiro Dos Santos Miggiolaro, James Monkman, Habib SadeghiRad, Dharmesh D. Bhuva, Jarbas da Silva Motta Junior, Caroline Busatta Vaz de Paula, Seigo Nagashima, Cristina Pellegrino Baena, Paulo Souza-Fonseca-Guimaraes, Lucia de Noronha, Timothy McCulloch, Gustavo Rodrigues Rossi, Caroline Cooper, Benjamin Tang, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca-Guimaraes, Gabrielle T. Belz, Ken O'Byrne
Summary: Spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment. This study used targeted transcriptomics of formalin-fixed paraffin-embedded tissue to examine the pulmonary transcriptional landscape of COVID-19 patients. The results showed significant upregulation of genes associated with inflammation, type I interferon production, coagulation, and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. Additionally, the study found that the gene IFI27, previously identified as a useful blood biomarker for differentiating bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Oncology
Luis G. Paz-Ares, Suresh S. Ramalingam, Tudor-Eliade Ciuleanu, Jong-Seok Lee, Laszlo Urban, Reyes Bernabe Caro, Keunchil Park, Hiroshi Sakai, Yuichiro Ohe, Makoto Nishio, Clarisse Audigier-Valette, Jacobus A. Burgers, Adam Pluzanski, Randeep Sangha, Carlos Gallardo, Masayuki Takeda, Helena Linardou, Lorena Lupinacci, Ki Hyeong Lee, Claudia Caserta, Mariano Provencio, Enric Carcereny, Gregory A. Otterson, Michael Schenker, Bogdan Zurawski, Aurelia Alexandru, Alain Vergnenegre, Judith Raimbourg, Kynan Feeney, Sang-We Kim, Hossein Borghaei, Kenneth John O'Byrne, Matthew D. Hellmann, Arteid Memaj, Faith Ellen Nathan, Judith Bushong, Phuong Tran, Julie R. Brahmer, Martin Reck
Summary: Nivolumab plus ipilimumab continues to demonstrate durable long-term efficacy in patients with advanced NSCLC, with a significant improvement in overall survival compared to chemotherapy. Immune-mediated adverse events occur early but can be managed with guideline-based treatment. Discontinuation of nivolumab plus ipilimumab due to adverse events does not impact the long-term benefits seen in all randomized patients.
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Immunology
Arutha Kulasinghe, Ning Liu, Chin Wee Tan, James Monkman, Jane E. Sinclair, Dharmesh D. Bhuva, David Godbolt, Liuliu Pan, Andy Nam, Habib Sadeghirad, Kei Sato, Gianluigi Li Bassi, Ken O'Byrne, Camila Hartmann, Anna Flavia Ribeiro Dos Santos Miggiolaro, Gustavo Lenci Marques, Lidia Zytynski Moura, Derek Richard, Mark Adams, Lucia de Noronha, Cristina Pellegrino Baena, Jacky Y. Suen, Rakesh Arora, Gabrielle T. Belz, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca Guimaraes, John F. Fraser
Summary: The study reveals distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection, with upregulation of genes associated with DNA damage and repair, heat shock, and macrophage infiltration in COVID-19 patients' cardiac tissues. In comparison, pH1N1 infection showed upregulation of interferon and complement pathways. This highlights the need for further understanding of the effects on extra-pulmonary organs, including the cardiovascular system, in COVID-19 patients.
Article
Medicine, General & Internal
Martin P. Barr, Anne-Marie Baird, Sophia Halliday, Petra Martin, Emma H. Allott, James Phelan, Greg Korpanty, Linda Coate, Cathal O'Brien, Steven G. Gray, Jane S. Y. Sui, Brian Hayes, Sinead Cuffe, Stephen P. Finn
Summary: Liquid biopsy has the potential to improve patient care in the diagnostic and therapeutic setting in non-small cell lung cancer (NSCLC). It can be used to monitor EGFR mutations and inflammatory markers as prognostic indicators in NSCLC.
Article
Biochemistry & Molecular Biology
Tabassum Khair Barbhuiya, Mark Fisher, Eric D. Boittier, Emma Bolderson, Kenneth J. O'Byrne, Derek J. Richard, Mark Nathaniel Adams, Neha S. Gandhi
Summary: The study investigates the mechanism of CDCA3 binding to APC/C-Cdh1 through the non-canonical ABBA-like motif. The research finds that H-bonds, hydrophobic and ionic interactions within the ABBA-like motif are crucial for the binding. Alanine mutations disrupt the structure of the linker region, leading to altered affinities and binding to alternate sites on Cdh1.
Article
Oncology
Lecia V. Sequist, James Chih-Hsin Yang, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Tony Mok, Sarayut Lucien Geater, Sergey Orlov, Chun-Ming Tsai, Michael Boyer, Wu-Chou Su, Jaafar Bennouna, Terufumi Kato, Vera Gorbunova, Ki Hyeong Lee, Riyaz Shah, Dan Massey, Victoria Zazulina, Mehdi Shahidi, Martin Schuler
Summary: The study compared the efficacy of chemotherapy with afatinib in the treatment of EGFR-mutated lung adenocarcinoma. Results showed that afatinib prolonged progression-free survival and improved the quality of life for patients, when compared with chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Mark N. Adams, Laura V. Croft, Aaron Urquhart, Mohamed Ashick Mohamed Saleem, Anja Rockstroh, Pascal H. G. Duijf, Patrick B. Thomas, Genevieve P. Ferguson, Idris Mohd Najib, Esha T. T. Shah, Emma Bolderson, Shivashankar Nagaraj, Elizabeth D. Williams, Colleen C. Nelson, Kenneth J. O'Byrne, Derek J. Richard
Summary: This study evaluated the role of hSSB1/NABP2 in modulating the cellular response to androgens and ionizing radiation in prostate cancer. The expression of hSSB1 in prostate cancer is correlated with genomic instability and it regulates pathways involved in cell cycle progression and transcription. Additionally, hSSB1 is involved in modulating androgen response through transcriptional regulation. Exploiting hSSB1 in prostate cancer treatment might improve patient outcomes in ADT and/or radiotherapy.
Article
Oncology
Ming Tang, Joshua T. Burgess, Mark Fisher, Didier Boucher, Emma Bolderson, Neha S. Gandhi, Kenneth J. O'Byrne, Derek J. Richard, Amila Suraweera
Summary: This study aimed to explore the binding pose of COMMD4-H2B and develop a H2B peptide that disrupts the COMMD4-H2B interaction, which could serve as a potential therapeutic target for non-small cell lung cancer (NSCLC).
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Sugandha Bhatia, Jennifer H. Gunter, Joshua Burgess, Mark N. Adams, Kenneth O'Byrne, Erik W. Thompson, Pascal H. G. Duijf
Summary: Epithelial-mesenchymal plasticity (EMP) is a characteristic of cancer that promotes invasion, metastasis, and therapy resistance. This study shows that non-cancerous human epithelial lung cells can spontaneously shift towards a mesenchymal-like state without genetic changes. This suggests that acquisition of metastasis-associated features may occur prior to genetic alterations and cancerous transformation.
TRANSLATIONAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Jiyoung Lee, Yeonjoo Kim, Paris Ataliotis, Hyung-Goo Kim, Dae-Won Kim, Dorothy C. Bennett, Nigel A. Brown, Lawrence C. Layman, Soo-Hyun Kim
Summary: WDR11 is an important gene associated with Kallmann syndrome and plays a role in reproductive system development. Its molecular mechanism is not fully understood. In this study, we found that WDR11 is required for the development of primordial germ cells (PGCs) by regulating both canonical and noncanonical Hedgehog signaling pathways. Loss of WDR11 affects PGC motility and proliferation through the noncanonical pathway, and also modulates the growth of somatic cells surrounding PGCs through the canonical pathway. We further discovered that WDR11 regulates ciliogenesis and interacts with IFT20 to regulate anterograde intraflagellar transport.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Julia K. Soo, Joanna T. Castle, Dorothy C. Bennett
Summary: This study reports the discovery of a synthetic peptide that can selectively kill human melanoma cells while being less toxic to normal cells. The peptide is derived from the target-binding site of the melanoma suppressor protein p16 and can induce apoptosis through a different pathway. The peptide also shows varying toxicity to other types of cancer cells.
Article
Biology
Zachariah P. Schuurs, Alexander P. Martyn, Carl P. Soltau, Sam Beard, Esha T. Shah, Mark N. Adams, Laura V. Croft, Kenneth J. O'Byrne, Derek J. Richard, Neha S. Gandhi
Summary: This study explores small molecules that bind to hSSB1, an important protein related to the survival of cancer cells. Through computational and experimental approaches, three small molecules were discovered that prevent hSSB1 from binding to DNA, potentially interfering with the cell's ability to repair DNA. Further research is needed to understand the interaction between these compounds and cells, and to develop them as selective hSSB1 inhibitors.
Article
Chemistry, Physical
Ming Tang, Amila Suraweera, Xuqiang Nie, Zilin Li, Pinglin Lai, James W. Wells, Kenneth J. O'Byrne, Robert J. Woods, Emma Bolderson, Derek J. Richard
Summary: In this study, the atomic-level mechanisms of Banf1-DNA binding and the effects of mono- and di-phosphorylation on Banf1's DNA-binding capability were explored using molecular modelling and dynamics simulations. It was found that mono-phosphorylation induces changes in Banf1's secondary structure, leading to the elimination of its DNA-binding capability. The study also demonstrated that phosphorylated Banf1 binds to DNA with lower affinity and less stable binding poses. These findings have implications for predicting the effects of Banf1 mutations on its DNA-binding capability and potential development of therapeutic drugs targeting cell proliferation.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Multidisciplinary Sciences
Thais Sobanski, Amila Suraweera, Joshua T. Burgess, Iain Richard, Chee Man Cheong, Keyur Dave, Maddison Rose, Mark N. Adams, Kenneth J. O'Byrne, Derek J. Richard, Emma Bolderson
Summary: This study reveals that the glycolytic protein ALDOA plays a direct role in DNA double-strand break (DSB) repair. Upon DNA damage, ALDOA translocates into the nucleus and associates with the DNA DSB marker γ-H2AX. Depletion of ALDOA leads to increased DNA damage before and slower repair after ionising radiation. It is suggested that targeting ALDOA may be a potential strategy for simultaneous disruption of cancer metabolism and DNA repair.
SCIENTIFIC REPORTS
(2023)