Editorial Material
Immunology
Lisa Rausch, Axel Kallies
Summary: Chromatin remodeling complexes cBAF and PBAF play a critical role in regulating the fate of CD8(+) T cells, including their proliferation, differentiation, and function in response to infection and cancer.
Article
Multidisciplinary Sciences
Francisco J. Sanchez-Rivera, Jeremy Ryan, Yadira M. Soto-Feliciano, Mary Clare Beytagh, Lucius Xuan, David M. Feldser, Michael T. Hemann, Jesse Zamudio, Nadya Dimitrova, Anthony Letai, Tyler Jacks
Summary: The level of mitochondrial apoptotic priming is a critical determinant of cell fate upon p53 reactivation, with cells having high initial priming tending to undergo apoptosis and cells with low priming tending to survive and arrest in the cell cycle. Manipulating the priming levels through BCL-2 or BCL-XL expression or inhibition can affect the outcome of p53 restoration, highlighting mitochondrial apoptotic priming as a key factor in determining cell fate. Moreover, less primed cells can be forced into apoptotic cell fate following p53 activation using p53-independent drugs that increase apoptotic priming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Elena Butturini, Giovanna Butera, Raffaella Pacchiana, Alessandra Carcereri de Prati, Sofia Mariotto, Massimo Donadelli
Summary: The wild-type p53 protein plays a crucial role in controlling cell growth to prevent neoplasm formation, but missense mutations in the TP53 gene can lead to structural and functional changes in the protein in more than half of all cancers. This dual role also extends to the regulation of the cell's redox state. Therapeutic opportunities targeting cysteines offer potential for modifying the structure and function of p53 mutant isoforms for anticancer treatments.
Review
Cell Biology
Aurelio Balsalobre, Jacques Drouin
Summary: Pioneer factors are transcription factors that can initiate the opening of closed chromatin. They play crucial roles in determining cell fate and cellular reprogramming, but their misexpression can have pathological consequences.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
News Item
Biochemistry & Molecular Biology
Adrian Janiszewski, Grigorios Georgolopoulos, Martina Balli, Paraskevi Athanasouli, Frederic Lluis, Vincent Pasque
Summary: Recent research has identified two chromatin regulators, Hdac3 and Dax1, which synergistically restrict the developmental potential of mouse embryonic stem cells and act as a lineage barrier to primitive endoderm formation.
Review
Biochemistry & Molecular Biology
Honghu Li, Qian Luo, Wei Shan, Shuyang Cai, Ruxiu Tie, Yulin Xu, Yu Lin, Pengxu Qian, He Huang
Summary: Hematopoietic stem cells (HSCs) can perceive both soluble signals and biomechanical inputs, with mechanotransduction playing a critical role in regulating their functions. However, the underlying molecular details of biomechanical regulation in HSCs are still poorly understood.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Tullia Maraldi, Cristina Angeloni, Cecilia Prata, Silvana Hrelia
Summary: This review highlights the role of NOX-derived ROS in stem cell biology and functions, focusing on the positive and negative effects triggered by the activity of different NOX isoforms. Recent findings on downstream molecular targets of NOX-ROS signaling that can modulate stem cell homeostasis and lineage commitment are discussed, along with implications in ex vivo expansion and in vivo engraftment, function, and longevity. The pivotal role of NOX as a regulator of several stem cell populations is underscored, and further studies on the effects of pharmacological modulation of NOX in human stem cells are deemed imperative.
Review
Biochemistry & Molecular Biology
Jared T. Field, Joseph W. Gordon
Summary: BNIP3 and Nix are atypical members of the BCL-2 family, which induce cell death through a transmembrane domain. In addition to cell death, they also play specific roles in metabolic stress, cell atrophy, and various forms of cell death. Recent studies have revealed their important functions in regulating cell fate.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Marika Sjoqvist, Daniel Antfolk, Freddy Suarez-Rodriguez, Cecilia Sahlgren
Summary: Intermediate filaments have emerged as important regulators of cellular signaling events, beyond providing structural support, by regulating cell differentiation and influencing cell fate decisions in conjunction with stem cell signaling pathways. Lack of IFs causes perturbed stem cell differentiation, and deregulation in these signaling pathways can result in various diseases. Studying the interaction and regulation of IFs with cell signaling helps expand our understanding of IF-linked diseases.
Review
Oncology
Vinesh Dhokia, John A. Y. Moss, Salvador Macip, Joanna L. Fox
Summary: Cellular senescence and apoptosis were historically considered as distinct cell fate pathways, but they share common proteins. p53 plays a key role in determining cell fate, but its decision-making process is not fully understood. Cell fate is dynamic and can be shifted by the right combination of activators and inhibitors. This review focuses on the regulation and induction of apoptosis and senescence, as well as their alterations in chronic diseases.
Review
Biochemistry & Molecular Biology
Agata Swiatkowska
Summary: p53 is a crucial transcription factor for maintaining cellular homeostasis, and its mutations are strongly linked to tumor development. Different isoforms of p53 have been identified, which can modulate its activity under stress conditions. In renal cancer, mutations in the VHL gene are associated with the most common subtype, renal cell carcinoma (RCC), and the VHL protein is essential for full activation of p53. Changes in the expression of p53 isoforms are associated with different stages of RCC and overall survival.
Article
Biology
Rabih Roufayel, Khaled Younes, Ahmed Al-Sabi, Nimer Murshid
Summary: Apoptosis is a crucial pathway for maintaining homeostasis, with BH3-only proteins Noxa and Puma playing important roles. These proteins are involved in physiological and pathological processes, such as immunity, cancer, and neurodegenerative diseases. Future research should focus on the impact of hyperthermia on Noxa and other BH3-only proteins, as well as the post-transcriptional mechanisms controlling the translation of Puma and Noxa mRNA.
Review
Biochemistry & Molecular Biology
Jana Riegger, Astrid Schoppa, Leonie Ruths, Melanie Haffner-Luntzer, Anita Ignatius
Summary: This article discusses oxidative stress as a major driver of pathophysiological processes in cartilage and bone, including aging, misdirected differentiation, cell death, mitochondrial dysfunction, and impaired mitophagy. It also elaborates on cellular defense mechanisms and therapeutic strategies to improve cell and tissue protection.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Mayra Colardo, Noemi Martella, Daniele Pensabene, Silvia Siteni, Sabrina Di Bartolomeo, Valentina Pallottini, Marco Segatto
Summary: Neurotrophins are a family of growth factors initially thought to primarily mediate nervous system development and neuronal survival, but increasing evidence suggests they also play crucial roles in regulating metabolic processes such as redox balance, glucose homeostasis, and cholesterol metabolism. This review examines the signaling pathways of neurotrophins and their impact on metabolism, particularly focusing on their effects on cholesterol metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Sydney Treichel, Marie-Dominique Filippi
Summary: Hematopoietic stem cells have the ability to self-renew or differentiate into various blood cell lineages. The cell fate decisions of self-renewal or differentiation must be tightly controlled to prevent diseases like bone marrow failure or leukemia. Studies have shown that the cell cycle length plays a crucial role in hematopoietic stem cell fate. Cell cycle kinetics, divisional history, asymmetric cell divisions, metabolic and organelle activity all have an impact on hematopoietic stem cell fate decisions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Guanglin Niu, Isabel Hellmuth, Tatiana Flisikowska, Hubert Pausch, Beate Rieblinger, Alexander Carrapeiro, Benjamin Schade, Brigitte Boehm, Eva Kappe, Konrad Fischer, Bernhard Klinger, Katja Steiger, Reiner Burgkart, Jean-Christophe Bourdon, Dieter Saur, Alexander Kind, Angelika Schnieke, Krzysztof Flisikowski
Summary: The mutation in TP53 gene in pig models leads to the development of tumors like osteosarcoma, pointing out similarities with human TP53. Specific TP53 isoforms determine the tumor spectrum in pigs, with circTP53 playing a critical role in malignant transformation.
Article
Biochemistry & Molecular Biology
Jayanthi P. Gudikote, Tina Cascone, Alissa Poteete, Piyada Sitthideatphaiboon, Qiuyu Wu, Naoto Morikawa, Fahao Zhang, Shaohua Peng, Pan Tong, Lerong Li, Li Shen, Monique Nilsson, Phillip Jones, Erik P. Sulman, Jing Wang, Jean-Christophe Bourdon, Faye M. Johnson, John Heymach
Summary: p53 inactivation is present in almost all tumors, making p53 reactivation strategies an important aspect of cancer therapy. Inhibition of nonsense-mediated decay (NMD) can upregulate p53 beta and p53 gamma levels, restore p53 pathway activation, and induce tumor suppressive activities. NMD inhibition is identified as a novel therapeutic strategy for restoration of p53 function in p53-deficient tumors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Nikola Arsic, Tania Slatter, Gilles Gadea, Etienne Villain, Aurelie Fournet, Marina Kazantseva, Frederic Allemand, Nathalie Sibille, Martial Seveno, Sylvain de Rossi, Sunali Mehta, Serge Urbach, Jean-Christophe Bourdon, Pau Bernado, Andrey Kajava, Antony Braithwaite, Pierre Roux
Summary: The p53 isoform Delta 133p53 beta promotes intrinsic oncogenic functions, with its activity regulated through an aggregation-dependent mechanism. Interaction with partners like p63 family members or the CCT chaperone complex influences cancer cell features such as migration and invasion by modulating Delta 133p53 beta activity.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Kevin Jan Legscha, Edite Antunes Ferreira, Antonios Chamoun, Alexander Lang, Mohamed Hemaid Sayed Awwad, Gigi Nu Hoang Quy Ton, Danuta Galetzka, Borhane Guezguez, Michael Hundemer, Jean-Christophe Bourdon, Markus Munder, Matthias Theobald, Hakim Echchannaoui
Summary: This study revealed a broad effect of the Delta 133p53 alpha isoform in regulating T lymphocyte function. Enhancing the fitness and effector functions of senescent T cells by modulating p53 isoforms could be utilized for future translational research to improve cancer immunotherapy and immunosenescence-related diseases.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Hematology
Elizabeta A. Rojas, Luis A. Corchete, Cristina De Ramon, Patryk Krzeminski, Dalia Quwaider, Ramon Garcia-Sanz, Joaquin Martinez-Lopez, Albert Oriol, Laura Rosinol, Joan Blade, Juan Jose Lahuerta, Jesus F. San Miguel, Marcos Gonzalez, Maria Victoria Mateos, Jean-Christophe Bourdon, Irena Misiewicz-Krzeminska, Norma C. Gutierrez
Summary: This study demonstrates for the first time the prognostic value of p53 isoforms in multiple myeloma patients, providing new insights into the role of p53 protein dysregulation in multiple myeloma biology.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sunali Mehta, Hamish Campbell, Catherine J. Drummond, Kunyu Li, Kaisha Murray, Tania Slatter, Jean-Christophe Bourdon, Antony W. Braithwaite
Summary: p53 is a crucial protein in maintaining biological homeostasis, with its network playing a vital role in maintaining stability within multicellular organisms, facilitating cooperation between cells to adapt to environmental changes.
Article
Oncology
Xiajie Zhang, Kira Groen, Brianna C. Morten, Luiza Steffens Reinhardt, Hamish G. Campbell, Antony W. Braithwaite, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
Summary: This study aimed to evaluate the role of Delta 40p53 in breast cancer migration and invasion, finding an association between Delta 40p53 and gene expression profiles. Knockdown of both p53 alpha and Delta 40p53 resulted in increased proliferation, while overexpression of Delta 40p53 reduced proliferation rates and decreased migratory and invasive properties of the cells. These results suggest that at a basal level, Delta 40p53 works similarly to p53 alpha in suppressing cellular mobility and proliferation.
MOLECULAR ONCOLOGY
(2022)
Article
Cell Biology
Yitian Guo, Melanie Rall-Scharpf, Jean-Christophe Bourdon, Lisa Wiesmuller, Stephanie Biber
Summary: This study demonstrates that different p53 isoforms have varying effects on the p53-POL iota-dependent DNA damage tolerance (DDT) pathway. Despite lacking the biochemical activities required for this pathway, all alternative isoforms exhibit impairments in promoting POL iota recruitment to PCNA and decelerating DNA replication.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Flora Nguyen Van Long, Audrey Lardy-Cleaud, Dimitri Carene, Caroline Rossoni, Frederic Catez, Paul Rollet, Nathalie Pion, Deborah Monchiet, Agathe Dolbeau, Marjorie Martin, Valentin Simioni, Susan Bray, Doris Le Beherec, Fernanda Mosele, Ibrahim Bouakka, Amelie Colombe-Vermorel, Laetitia Odeyer, Alexandra Diot, Lee B. Jordan, Alastair M. Thompson, Francoise Jamen, Thierry Dubois, Sylvie Chabaud, Stefan Michiels, Isabelle Treilleux, Jean-Christophe Bourdon, David Perol, Alain Puisieux, Fabrice Andre, Jean-Jacques Diaz, Virginie Marcel
Summary: FBL has been identified as a powerful independent marker of breast cancer prognosis related to ribosome biogenesis. Surprisingly, low activation of ribosome biogenesis is also associated with poor outcome.
Article
Biochemistry & Molecular Biology
Luiza Steffens Reinhardt, Kira Groen, Brianna C. Morten, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
Summary: TP53 mutations are associated with tumor progression, therapy resistance, and poor prognosis in breast cancer. However, other mechanisms, such as p53 isoform dysregulation, may contribute to the disruption of the p53 pathway. This study found that high levels of p53 beta, a N-terminally truncated variant, were significantly associated with worse disease-free survival, especially in tumors with wild-type TP53, suggesting that p53 beta may serve as a prognostic marker in breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Muyang Li, Fredrick Philantrope, Alexandra Diot, Jean-Christophe Bourdon, Patricia Thompson
Summary: In this study, we found that inhibition of SMG1 in MCF7 tumor cells induces increased expression of p53 beta and p53 gamma, as well as upregulation of several cholesterol pathway genes. Our study also revealed that silencing SMG1 leads to increased expression of ABCA1, a cholesterol efflux pump, and this may be related to the differential effects of p53 isoforms on cholesterol gene expression.
Article
Cell Biology
Luiza Steffens Reinhardt, Xiajie Zhang, Kira Groen, Brianna C. Morten, Geoffry N. De Iuliis, Antony W. Braithwaite, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
Summary: This study found that the response of breast cancer cells to DNA-damaging therapies in standard care is dependent on the expression of p53 isoforms. A high Delta 40p53:p53 alpha ratio causes cells to respond differently to doxorubicin and cisplatin treatments, increasing resistance to doxorubicin and promoting DNA repair, thereby impairing the cells' normal response.
CELL DEATH & DISEASE
(2022)
Meeting Abstract
Oncology
K. Legscha, E. Antunes, M. Awwad, G. Ton, G. Borhane, M. Hundemer, J. -C Bourdon, M. Theobald, H. Echchannaoui
ONCOLOGY RESEARCH AND TREATMENT
(2021)
Meeting Abstract
Oncology
Xiajie Zhang, Kira Groen, Brianna C. Morten, Luiza Steffens Reinhardt, Hamish G. Campbell, AntonyW. Braithwaite, Jean-Christophe Bourdon, Kelly A. Avery-Kiejda
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
(2021)
Correction
Biochemistry & Molecular Biology
Virginie Marcel, Janice Kielbassa, Virginie Marchand, Kundhavai S. Natchiar, Hermes Paraqindes, Flora Nguyen Van Long, Lilia Ayadi, Valerie Bourguignon-Igel, Piero Lo Monaco, Deborah Monchiet, Veronique Scott, Laurie Tonon, Susan E. Bray, Alexandra Diot, Lee B. Jordan, Alastair M. Thompson, Jean-Christophe Bourdon, Thierry Dubois, Fabrice Andre, Frederic Catez, Alain Puisieux, Yuri Motorin, Bruno P. Klaholz, Alain Viari, Jean-Jacques Diaz
