Article
Plant Sciences
Hongbo Li, Juan Wei, Yanglan Liao, Xiaoling Cheng, Shuhong Yang, Xiaohong Zhuang, Zhonghui Zhang, Wenjin Shen, Caiji Gao
Summary: This study reveals a previously unidentified function of plant-specific casein kinase I members in attenuating ABA signaling by regulating the phosphorylation and nuclear accumulation of FREE1.
PLANT CELL AND ENVIRONMENT
(2022)
Article
Neurosciences
Mingming Yang, Rongrong Qi, Yuxiao Liu, Xin Shen, Yulou Zhao, Nana Jin, Ruozhen Wu, Fei Liu, Jianlan Gu
Summary: In this study, it was discovered that the elevated levels of CK1δ in the brain of Alzheimer's disease (AD) patients contribute to the phosphorylation and aggregation of TDP-43. Furthermore, CK1δ overexpression inhibits the activity of TDP-43 in promoting tau mRNA instability and E10 inclusion. These findings suggest that CK1δ plays a significant role in the pathologies of TDP-43 and tau in AD.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Biochemistry & Molecular Biology
John E. Chojnowski, Rongrong Li, Tiffany Tsang, Fatimah H. Alfaran, Alexej Dick, Simon Cocklin, Donita C. Brady, Todd I. Strochlic
Summary: Casein kinase 2 (CK2) is an evolutionarily conserved enzyme involved in cellular functions, and its dysregulation is linked to diseases like cancer. This study demonstrates that copper enhances CK2 activity by binding directly to the enzyme. Specific residues in the catalytic subunit are critical for copper-binding. Changes in cellular copper levels also affect CK2 activity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cell Biology
Francesca Zonta, Christian Borgo, Camila Paz Quezada Meza, Ionica Masgras, Andrea Rasola, Mauro Salvi, Lorenzo A. Pinna, Maria Ruzzene
Summary: CK2, an overexpressed Ser/Thr protein kinase in many cancers, plays a crucial role in the uncontrolled proliferation, motility, and survival of cancer cells. This study reveals that both CK2 alpha and alpha' isoforms contribute to cell proliferation, survival, and tumorigenicity, with a prominent role for CK2 alpha in tumor metabolism.
Review
Biochemistry & Molecular Biology
May-Britt Firnau, Angela Brieger
Summary: In this study, evidence from literature is compiled to suggest that CK2 modulates all hallmarks of cancer, thereby promoting oncogenesis and operating as a cancer driver by creating a cellular environment favorable to neoplasia.
Article
Biochemistry & Molecular Biology
Fredrick J. Rosario, Anand Chopra, Kyle Biggar, Theresa L. Powell, Madhulika B. Gupta, Thomas Jansson
Summary: The mechanisms underlying restricted growth in intrauterine growth restriction (IUGR) are not fully understood. The mTOR signaling pathway acts as a placental nutrient sensor and indirectly affects fetal growth by regulating placental function. In this study, we found that inhibition of trophoblast mTOR increased the secretion and phosphorylation of liver IGFBP-1, which decreased the bioavailability of IGF-1 and inhibited fetal growth. This suggests that placental mTOR signaling may play a role in regulating fetal growth by controlling liver IGFBP-1 phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
K. Chojnacki, D. Lindenblatt, P. Winska, M. Wielechowska, C. Toelzer, K. Niefind, M. Bretner
Summary: New halogenated 1H-triazolo [4,5-b] pyridines and 1H-imidazo [4,5-b] pyridines were synthesized as analogues of known CK2 inhibitors, with di- and trihalogenated 1H-triazolo [4,5-bl] pyridines showing the highest activity against CK2 alpha. Compounds were also evaluated for their effect on the viability of cancer cell lines, and crystal structures of complexes with CK2 alpha and CK2 alpha' were obtained.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Nhu Nguyen Quynh Tran, Kwang-Hoon Chun
Summary: KD025 is a ROCK2 isoform-specific inhibitor that inhibits adipocyte differentiation by inhibiting CK2. It shows comparable binding affinity to CK2 alpha and effectively inhibits CK2 at nanomolar concentrations. Both CX-4945 and KD025 act specifically in the middle stage of adipocyte differentiation, indicating that they may regulate the same target, CK2.
Article
Chemistry, Medicinal
Alexander Schnitzler, Karsten Niefind
Summary: CK2, a Ser/Thr kinase, has a specific acidic substrate recognition sequence and is inhibited by polyanionic substances like heparin. This study describes the crystal structures of CK2 in complex with different heparin fragments, which provide insights into the inhibitory mechanism of heparin fragments and their chain length-dependent efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Sabrin R. M. Ibrahim, Alaa A. Bagalagel, Reem M. Diri, Ahmad O. Noor, Hussain T. Bakhsh, Yosra A. Muhammad, Gamal A. Mohamed, Abdelsattar M. Omar
Summary: In this study, the CK2 inhibitory activity of 33 fungal phenalenones was explored using computational studies. Compound 19 showed higher binding affinity and made additional contacts with distant amino acid residues from the active site.
Article
Chemistry, Medicinal
Zachary W. Davis-Gilbert, Andreas Kraemer, James E. Dunford, Stefanie Howell, Filiz Senbabaoglu, Carrow I. Wells, Frances M. Bashore, Tammy M. Havener, Jeffery L. Smith, Mohammad A. Hossain, Udo Oppermann, David H. Drewry, Alison D. Axtman
Summary: Naphthyridine-based inhibitors were synthesized to produce a potent and cell active inhibitor of casein kinase 2 (CK2). Compound 2 selectively inhibits CK2 alpha and CK2 alpha ' when broad-profiled, making it an exquisitely selective chemical probe for CK2. A negative control, compound 7, lacking a key hinge-binding nitrogen, was designed based on structural studies and showed excellent kinome-wide selectivity by not binding CK2 alpha or CK2 alpha ' in cells. Compound 2 displayed differential anticancer activity compared to a structurally distinct CK2 chemical probe, SGC-CK2-1.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Scott E. Roffey, David W. Litchfield
Summary: CK2, an acidophilic serine/threonine kinase, regulates various biological processes such as apoptosis and cell proliferation. Studies have linked CK2 to human malignancies and diseases, but the mechanisms regulating CK2 activity remain incompletely understood.
Review
Cell Biology
Stefano Sechi, Roberto Piergentili, Maria Grazia Giansanti
Summary: Cytokinesis, the final stage of cell division, plays a crucial role in normal development and preventing cancer. Kinase-mediated phosphorylation is a key process in regulating cytokinesis. While some kinases have well-established roles, others have been less studied but may uncover new pathways of cell division regulation.
Article
Pharmacology & Pharmacy
Julia E. Fux, Emilie C. Lefort, Praveen P. N. Rao, Jonathan Blay
Summary: The dietary flavone apigenin upregulates CD26 on colorectal carcinoma cells and shows a synergistic interaction with the chemotherapeutic agent irinotecan. Apigenin inhibits topoisomerase 1 activity, which may limit local signals that facilitate tumor progression.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Katharina Ulreich, May-Britt Firnau, Nina Tagscherer, Sandra Beyer, Anne Ackermann, Guido Plotz, Angela Brieger
Summary: High nuclear/cytoplasmic expression of CK2 alpha in colorectal cancer correlates with enhanced MLH1 phosphorylation and may cause increased mutation rates. These findings suggest important new therapeutic targets.
Article
Fisheries
Fatma Hermi, Victoria Gomez-Abellan, Ana B. Perez-Oliva, Diana Garcia-Moreno, Azucena Lopez-Munoz, Elena Sarropoulou, Marta Arizcun, Oueslati Ridha, Victoriano Mulero, Maria P. Sepulcre
Summary: This study identified and characterized prostaglandin E-2 receptors in gilthead seabream and found differential expression patterns in various tissues and immune cells. The results suggest distinct roles for these receptors in regulating immune responses.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Cell Biology
Francesca Zonta, Christian Borgo, Camila Paz Quezada Meza, Ionica Masgras, Andrea Rasola, Mauro Salvi, Lorenzo A. Pinna, Maria Ruzzene
Summary: CK2, an overexpressed Ser/Thr protein kinase in many cancers, plays a crucial role in the uncontrolled proliferation, motility, and survival of cancer cells. This study reveals that both CK2 alpha and alpha' isoforms contribute to cell proliferation, survival, and tumorigenicity, with a prominent role for CK2 alpha in tumor metabolism.
Article
Biology
Karen Dunbar, Thomas J. Macartney, Gopal P. Sapkota
Summary: IMiDs bind to CRBN to recruit and degrade specific proteins like FAM83F, which interacts with CK1 alpha. The efficiency of target protein degradation by IMiDs depends on the nature of the multiprotein complex the protein is part of, as shown by the protective role of FAM83G on CK1 alpha degradation.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biology
Karen Dunbar, Rebecca A. Jones, Kevin Dingwell, Thomas J. Macartney, James C. Smith, Gopal P. Sapkota
Summary: FAM83F protein interacts with CK1 alpha at the plasma membrane to activate Wnt signaling, leading to axis duplication in Xenopus embryos, and its effects on Wnt signaling are mediated through farnesylation at the plasma membrane.
LIFE SCIENCE ALLIANCE
(2021)
Article
Chemistry, Medicinal
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. Pinna
Summary: CK2, a protein kinase with pleiotropic functions, is implicated in global human pathologies, particularly cancer. Selective inhibitors like CX4945 and GO289 show promise in controlling the CK2-dependent phosphoproteome.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Peter Stacey, Hannah Lithgow, Xiao Lewell, Agnieszka Konopacka, Stephen Besley, Georgina Green, Ryan Whatling, Robert Law, Sascha Roeth, Gopal P. Sapkota, Ian E. D. Smith, Glenn A. Burley, John Harling, Andrew B. Benowitz, Markus A. Queisser, Marcel Muelbaier
Summary: A novel phenotypic screening approach was utilized to identify E3 ligase binders and generate functional HaloPROTACs for the degradation of fusion proteins in living cells. This method offers an important tool for further development of PROTACs.
Review
Medicine, General & Internal
Maria Sanchez-Villalobos, Miguel Blanquer, Jose M. Moraleda, Eduardo J. Salido, Ana B. Perez-Oliva
Summary: In this article, the main pathophysiological pathways involved in beta-thalassemia are reviewed, with a focus on the development of new therapies directed at new therapeutic targets.
FRONTIERS IN MEDICINE
(2022)
Article
Fisheries
Juan M. Lozano-Gil, Lola Rodriguez-Ruiz, Sylwia D. Tyrkalska, Diana Garcia-Moreno, Ana B. Perez-Oliva, Victoriano Mulero
Summary: This study utilized a zebrafish model to show that inhibition of myeloid cell inflammasome led to an increase in specific immune cells during inflammation. The findings suggest that myeloid inflammasome autonomously regulates pyroptotic cell death in chronic inflammation through a Gasdermin E-dependent pathway.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2022)
Review
Cell Biology
Sambit K. Nanda, Stefan Vollmer, Ana B. Perez-Oliva
Summary: This review summarizes classical post-translational modifications (PTMs) such as phosphorylation, ubiquitylation, and SUMOylation of the different components of NLRP3 and other emerging inflammasomes. The importance of these modifications in the biology, function, and regulation of these multiprotein complexes in various immune processes and human diseases is highlighted. Less-studied modifications and disease-associated mutations affecting PTMs are also discussed. The review concludes by emphasizing how a deeper understanding of different PTMs can contribute to the development of biomarkers and identification of novel drug targets for diseases associated with inflammasome malfunctioning.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Belen Fatas-Lalana, Joaquin Canton-Sandoval, Lola Rodriguez-Ruiz, Raul Corbalan-Velez, Teresa Martinez-Menchon, Ana B. Perez-Oliva, Victoriano Mulero
Summary: A retrospective study in a Spanish cohort of 200 psoriasis patients and 100 healthy donors investigated the comorbidities associated with psoriasis and their impact on phototherapy response. The study found a higher incidence of various comorbidities in psoriasis patients, particularly in those over 40 years old. Phototherapy was effective in treating moderate-severe psoriasis, with narrow-band ultraviolet B being the most effective type. However, comorbidities such as liver disease, hypertension, heart disease, vascular disease, and diabetes were associated with a lower response to phototherapy. Liver disease and anemia comorbidities were found to favor treatment failure. Additionally, zebrafish and human 3D organotypic models suggested the potential therapeutic benefit of inhibiting GLUT1 and dipeptidyl peptidase 4 for psoriasis. Identifying specific comorbidities is crucial when planning treatment for psoriasis patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Hematology
Elena Martinez-Balsalobre, Jean-Hugues Guervilly, Jenny van Asbeck van der Wijst, Ana Belen Perez-Oliva, Christophe Lachaud
Summary: Fanconi anemia is a rare inherited disorder that affects the bone marrow and leads to decreased production of blood cells. Defective repair of DNA interstrand crosslinks is one of the causes, with mutations in over 20 genes linked to the disease. Advances in science and molecular biology have shed light on the relationship between FA gene mutations and the severity of clinical manifestations. This article highlights the current and promising therapeutic options for this rare disease.
Article
Biochemistry & Molecular Biology
Lorenzo Badenetti, Rosa Manzoli, Michela Rubin, Giorgio Cozza, Enrico Moro
Summary: Among cytoprotective mechanisms, eukaryotic cells rely on the Nrf2 transcription factor to initiate a complex transcriptional program during biological stressors, including oxidative stress. Nrf2 has recently been found to play a crucial role in various research fields, such as cancer, inflammatory disorders, and age-related neurological diseases. In this study, a novel Nrf2/ARE pathway biosensor fish was generated and characterized, demonstrating spatiotemporal expression during early development. This transgenic fish shows responsiveness to Nrf2 pathway modulators and Edaravone, which has not been seen in any live transgenic fish models before. The activated reporter in this fish is also shown to be faithful during fin regeneration and slightly affected in a glucocerebrosidase morphant zebrafish model. Therefore, this innovative transgenic fish can serve as a valuable tool for studying zebrafish models of human diseases and primary high-throughput drug screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Giulia Nordio, Francesco Piazzola, Giorgio Cozza, Monica Rossetto, Manuela Cervelli, Anna Minarini, Filippo Basagni, Elisa Tassinari, Lisa Dalla Via, Andrea Milelli, Maria Luisa Di Paolo
Summary: Monoamine oxidases (MAOs) have been widely studied in neurological diseases, but recent research has discovered their potential role in certain types of cancer. This study identified novel MAO inhibitors with antiproliferative activity, suggesting their potential as anticancer agents.
Article
Biochemistry & Molecular Biology
Luke M. Simpson, Luke J. Fulcher, Gajanan Sathe, Abigail Brewer, Jin-Feng Zhao, Daniel R. Squair, Jennifer Crooks, Melanie Wightman, Nicola T. Wood, Robert Gourlay, Joby Varghese, Renata F. Soares, Gopal P. Sapkota
Summary: Reversible protein phosphorylation is crucial for controlling protein function and intracellular signaling. This study presents the development and application of the AdPhosphatase system, which allows targeted dephosphorylation of specific phospho-substrates. By using antigen-stabilized anti-GFP nanobody conjugated with Protein Phosphatase 1 or 2A catalytic subunits, the researchers successfully achieved specific dephosphorylation of two phospho-proteins, FAM83D and ULK1, with exquisite specificity. AdPhosphatase provides a new modality for potential drug discovery approaches by altering the phospho-status and function of target proteins.
CELL CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Luke M. Simpson, Lorraine Glennie, Abigail Brewer, Jin-Feng Zhao, Jennifer Crooks, Natalia Shpiro, Gopal P. Sapkota
Summary: This study investigates whether the subcellular context of a protein of interest (POI) affects the efficacy of PROTAC-mediated protein degradation. The results suggest that the subcellular localization of the POI can influence the effectiveness of PROTAC-induced POI degradation.
CELL CHEMICAL BIOLOGY
(2022)
