Article
Biochemistry & Molecular Biology
Siobhan O'Brien, Susan Kelso, Zachary Steinhart, Stephen Orlicky, Monika Mis, Yunhye Kim, Sichun Lin, Frank Sicheri, Stephane Angers
Summary: This study reports a novel synthetic lethal genetic interaction between FBXW7 and CCNL1 and identifies CCNL1 as a substrate of the SCF-FBXW7 E3 ligase. Defective CCNL1 accumulation resulting from FBXW7 mutation leads to shorter mitotic time. Cells with FBXW7 loss-of-function mutations are highly sensitive to treatment with a CDK11 inhibitor, suggesting a potential genetic vulnerability for cancer treatment.
Article
Oncology
Swapna Asuthkar, Sujatha Venkataraman, Janardhan Avilala, Katherine Shishido, Rajeev Vibhakar, Bethany Veo, Ian J. Purvis, Maheedhara R. Guda, Kiran K. Velpula
Summary: Medulloblastoma (MB) is the most common malignant pediatric brain tumor, and the standard of care for MB patients includes maximum safe resection, postoperative craniospinal irradiation, and chemotherapy. Recent research has identified SMYD3 as a crucial epigenetic regulator, which activates the transcription of cyclin D3 and drives the growth of Group 3 Myc+ MB cells.
Review
Oncology
Yosuke Funato, Osamu Hashizume, Hiroaki Miki
Summary: Phosphatase of regenerating liver (PRL) is a family of protein tyrosine phosphatases (PTPs) that are overexpressed in malignant cancers. They bind to CNNM Mg2+ exporters in the plasma membrane, inhibiting their activity and increasing intracellular Mg2+ levels. Dysregulation of Mg2+ levels affects ATP, reactive oxygen species (ROS), and Ca2+-permeable channels, contributing to cancer progression.
Article
Biochemistry & Molecular Biology
Ilona Faustova, Luka Bulatovic, Frida Matiyevskaya, Ervin Valk, Mihkel Ord, Mart Loog
Summary: Cyclin-dependent kinases (CDKs) are regulated by different cyclins throughout the cell cycle, with the NLxxxL docking motif playing a crucial role in the phosphorylation-dependent degradation of the CDK inhibitor Far1 at the G1/S stage in yeast. This motif is specifically recognized by the S-phase CDK (S-CDK) Clb5/6-Cdc28, indicating its importance in controlling cell cycle events. Additionally, the NLxxxL motif governs S-cyclin-specificity in multiple yeast CDK targets, suggesting its significance in fine-tuning cell cycle processes.
Article
Plant Sciences
Sophie Hendrix, Rossella Alfano, Michelle Plusquin, Ann Cuypers
Summary: Cadmium exposure has different effects on individual leaves in Arabidopsis thaliana, with the leaf emerged during Cd exposure showing the most similar response to the regulation of the DNA damage response and cell cycle progression observed in the entire rosette. This finding is important for interpreting rosette data in the context of plant development and response to Cd exposure.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Oncology
Jiajun Zhao, Zhen Zhang, Tantan Zuo, Jie Yu, Shihao Yang, Yitao Yang, Xinqi Li, Jia Zheng
Summary: The study found that miR-892b antagomir inhibits the progression of osteoarthritis (OA) by targeting Cyclin D1 and Cyclin D2, serving as a novel target for OA treatment.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Microbiology
Dorothee Serian, Yury Churin, Jens Andre Hammerl, Manfred Rohde, Arne Jung, Anja Mueller, Min Yue, Corinna Kehrenberg
Summary: In this study, seven Bordetella avium phages were isolated and characterized, showing broad host range and strong bacteriolytic activity. These phages used lipopolysaccharides as host receptors and exhibited a myovirus structure. Although phenotypically thought to be lytic, these phages were found to undergo a lysogenic phase, but infection did not confer stable host superinfection immunity. These findings are important for potential phage therapy against avian bordetellosis.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biotechnology & Applied Microbiology
Haoran Wang, Zixiang Liu, Peng Wu, Hanging Wang, Weiwei Ren
Summary: In osteosarcoma, upregulated NUSAP1 accelerates cell proliferation and cell cycle progression by binding to CDC20 and CCNA2, exacerbating tumor development.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Qiuyang Chen, Yue Fu, Xinchun Liu, Peng Wang, Shangnan Dai, Feng Zhu, Tongtai Liu, Wenbin Xu, Junli Wu
Summary: This study investigated the functional role of CKS2 in pancreatic cancer and found that high expression of CKS2 was associated with poor prognosis. Functional assays showed that CKS2 knockdown suppressed cell proliferation, induced cell cycle arrest and apoptosis, and reduced tumor growth. Furthermore, ELK1 protein was found to regulate transcription of the CKS2 gene. Therefore, CKS2 may serve as a prognostic indicator and therapeutic target for pancreatic cancer.
MOLECULAR CARCINOGENESIS
(2023)
Article
Oncology
Yue Xiao, Xinyi Chen, Weiwei Hu, Wenjing Ma, Qianqian Di, Haimei Tang, Xibao Zhao, Guodong Huang, Weilin Chen
Summary: The research finds that USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1. The overexpression of USP39 promotes the proliferation of human glioma cells and is positively correlated with the expression levels of Cyclin B1. The study suggests that USP39 is a novel deubiquitinating enzyme of Cyclin B1 and promotes tumor cell proliferation through Cyclin B1 stabilization.
TRANSLATIONAL ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Dharambir Kashyap, Vivek Kumar Garg, Elise N. Sandberg, Neelam Goel, Anupam Bishayee
Summary: Cancer, a disease of inappropriate cell proliferation, is closely linked to the cell cycle, with multiple genetic alterations leading to cancer development. Both oncogenes and tumor suppressor genes regulate the cell cycle and play key roles in breast cancer progression. These components are tightly controlled in normal breast epithelial cells, but following mitogenic stimuli, their deregulation promotes neoplastic transformation. Numerous clinical studies have revealed prognostic significance in screening for these components, impacting patient outcomes and treatment responses. The review aims to summarize the roles of oncogenic and tumor-suppressive components in breast cancer progression and prognosis.
Editorial Material
Cell Biology
Emiliano Maiani, Giacomo Milletti, Francesco Cecconi
Summary: AMBRA1 is a key scaffold protein that regulates early autophagosome formation, cell growth, and G1/S phase transition, and its deficiency is associated with neurodevelopmental defects and cancer. By controlling the expression of D-type cyclins, AMBRA1 plays a crucial role in maintaining genome integrity during DNA replication and represents a novel mechanism of cell cycle regulation interconnected with genomic stability in development and cancer.
Article
Surgery
Cansu Karakas, Ashleigh M. Francis, Min Jin Ha, Hannah F. Wingate, Richard A. Meena, Min Yi, Komal S. Rasaputra, Angelica M. Gutierrez Barrera, Banu Arun, Kim-Anh Do, Aysegul Sahin, Khandan Keyomarsi, Kelly K. Hunt
Summary: The presence of cytoplasmic cyclin E expression in breast cancer patients is associated with a lower rate of pathologic complete response to neoadjuvant chemotherapy and poorer long-term outcomes, making it a potential predictor for treatment response.
Review
Cell Biology
Rafaela Fagundes, Leonardo K. Teixeira
Summary: DNA replication must be precisely controlled, and cell cycle transitions are regulated by the Cyclin-Dependent Kinases (CDKs) family. The Cyclin E/CDK2 complex controls cell cycle progression and DNA replication through phosphorylation of specific substrates in normal cycles, while its oncogenic activation causes replication stress and genomic instability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Plant Sciences
Sorin Tanasa, Neha Shukla, Albert Cairo, Ranjani S. Ganji, Pavlina Mikulkova, Sona Valuchova, Vivek K. Raxwal, Claudio Capitao, Arp Schnittger, Zbynek Zdrahal, Karel Riha
Summary: Meiosis is a specialized cell division that reduces the number of chromosomes, followed by mitotic divisions to form haploid gametophytes in angiosperm plants. In Arabidopsis, the termination of meiosis and transition to gametophytic development are regulated by TDM1 and SMG7, which inhibit translation. Mutants deficient in this mechanism show aberrant nuclear divisions due to the failure to downregulate cyclin dependent kinases during meiotic exit. A mutation in cyclin-dependent kinase D;3 (CDKD;3) was identified as a suppressor that alleviates meiotic defects in smg7 deficient plants by preventing aberrant meiotic divisions or delaying their onset. CDKD;3 acts independently of CDKA;1 and interacts with proteins involved in cytokinesis, suggesting a complex role in cell cycle regulation.
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen
Review
Nutrition & Dietetics
Bodo C. C. Melnik, Swen Malte John, Pedro Carrera-Bastos, Loren Cordain, Claus Leitzmann, Ralf Weiskirchen, Gerd Schmitz
Summary: This review evaluates the impact of cow milk on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer pathogenesis. Recent prospective cohort studies support the association between cow's milk consumption and the risk of estrogen receptor-alpha-positive breast cancer. Milk contains various components that can increase systemic insulin-like growth factor 1, insulin, and estrogen signaling, promoting breast cancer. Potential oncogenic components of commercial milk include exosomal microRNAs, bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with certain gene mutations and genetic polymorphisms may be at increased risk for milk-induced breast cancer.
CURRENT NUTRITION REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Pierluigi Ramadori, Marius Maximilian Woitok, Olga Estevez-Vazquez, Raquel Benede-Ubieto, Hector Leal-Lassalle, Arantza Lamas-Paz, Feifei Guo, Jeanne Fabre, Julia Otto, Anna Verwaayen, Johanna Reissing, Tony Bruns, Stephanie Erschfeld, Ute Haas, Daniela Paffen, Leonard J. Nelson, Javier Vaquero, Rafael Banares, Christian Trautwein, Francisco Javier Cubero, Christian Liedtke, Yulia A. Nevzorova
Summary: Cyclin E1 plays a crucial role in liver fibrosis and hepatocarcinogenesis. The study investigated its role in alcohol-associated liver disease (ALD). The results showed that the lack of Cyclin E1 in hepatocytes worsens liver damage and leads to body weight loss.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Pharmacology & Pharmacy
Guoxun Chen, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Vitamin A is a micronutrient that plays crucial roles in vision, cell growth, reproduction, and immunity. Deficiency and excess consumption of vitamin A both have severe health consequences. Despite being the first lipophilic vitamin discovered over a century ago and the definition of its biological roles, there are still unresolved issues related to vitamin A.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Sandro Capellmann, Roland Sonntag, Herdit Schueler, Steffen K. Meurer, Lin Gan, Marlies Kauffmann, Katharina Horn, Hiltrud Koenigs-Werner, Ralf Weiskirchen, Christian Liedtke, Michael Huber
Summary: Mast cells (MCs) are heterogeneous immune cells with different protease repertoires and receptor expressions. A new cell line, PMC-306, derived from primary peritoneal MCs, can be used to study PMC function and tumorigenic processes associated with MC leukemia.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Cell Biology
Ralf Weiskirchen
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Erawan Borkham-Kamphorst, Steffen K. Meurer, Ralf Weiskirchen
Summary: The CCN protein family plays important biological functions in cell adhesion, migration, cell cycle progression, and control of extracellular matrix production and degradation. In the liver, CCN proteins are particularly involved in hepatic injury, disease, and remodeling. This study focused on CCN5/WISP2 and found that it is highly expressed in hepatic stellate cells, myofibroblasts, and portal myofibroblasts, while it is absent in hepatocytes. CCN5 upregulation during hepatic fibrosis induces endoplasmic reticulum stress, unfolded protein response, and apoptosis in portal myofibroblasts, potentially acting as a control mechanism against excessive fibrotic responses.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Kiara Gaeberlein, Sarah K. Schroeder, Indrajit Nanda, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Patrick Sauvant, Vincent Sapin, Armand Abergel, Ralf Weiskirchen
Summary: The rat hepatic stellate cell line PAV-1, established two decades ago, is a cellular model for studying hepatic retinoic acid metabolism. Despite being able to store retinyl esters and synthesize retinoic acid, this cell line has been overlooked. Genetically characterized established cell lines, like PAV-1, are valuable for biomedical research as working with in vivo models becomes more complicated.
Review
Cell Biology
Sabine Weiskirchen, Sarah K. K. Schroeder, Eva Miriam Buhl, Ralf Weiskirchen
Summary: The cultivation of cells in a favorable artificial environment has become an essential tool in cellular and molecular biology research. However, cell lines are often affected by misidentification, contamination, and specific biological and chemical hazards. This review offers an introduction to common problems encountered in cell culture laboratories and provides guidelines for preventing and addressing these issues.
Article
Cell Biology
Julia Otto, Anna Verwaayen, Christian Penners, Jana Hundertmark, Cheng Lin, Carina Kallen, Daniela Paffen, Tobias Otto, Hilmar Berger, Frank Tacke, Ralf Weiskirchen, Yulia A. Nevzorova, Matthias Bartneck, Christian Trautwein, Roland Sonntag, Christian Liedtke
Summary: Hepatocellular carcinoma (HCC) is a severe malignancy with limited treatment options. The development of HCC involves chronic liver inflammation and liver fibrosis. This study reveals the role of Cyclin E1 (CCNE1) and Cdk2 genes in Hepatic Stellate Cells (HSCs) in liver fibrogenesis and hepatocarcinogenesis.
CELL DEATH & DISEASE
(2023)
Review
Immunology
Sarah K. Schroeder, Natalie Gasterich, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Human 25-kDa Lipocalin 2 (LCN2) was initially thought to be a circulating protein that transports small lipophilic molecules. However, further studies have shown its bacteriostatic properties, involvement in innate immunity, and regulation of various biological processes. The understanding of LCN2 receptors and their mechanisms is still lacking.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ralf Weiskirchen, Sarah K. Schroeder, Sabine Weiskirchen, Eva Miriam Buhl, Bodo Melnik
Summary: Extracellular vesicles, such as exosomes, are small bilayered biovesicles released by cells, enriched with biologically active components. Milk exosomes play a key role in infant growth and development, while exosomes derived from different cell types have regenerative and immunomodulatory properties. Isolation protocols for milk exosomes allow the purification of highly enriched fractions, expressing typical exosomal protein markers.
Article
Biochemistry & Molecular Biology
Marinela Krizanac, Paola Berenice Mass Sanchez, Sarah K. Schroeder, Ralf Weiskirchen, Anastasia Asimakopoulos
Summary: Perilipin 5 (PLIN5) is a lipid droplet coat protein highly expressed in oxidative tissues. It is regulated by peroxisome proliferator-activated receptors (PPARs) and cellular lipid status. Previous research focused on its role in non-alcoholic fatty liver disease (NAFLD) and lipid metabolism regulation. Limited studies connected PLIN5 to hepatocellular carcinoma (HCC), where its expression is upregulated. This study explores the regulation of PLIN5 by cytokines involved in HCC and NAFLD progression, revealing IL-6-induced upregulation mediated by the JAK/STAT3 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen