Review
Cell Biology
Qian Li, Nengxian Shi, Chen Cai, Mingming Zhang, Jing He, Ying Tan, Weijun Fu
Summary: Pyroptosis is a gene-regulated cell death process dependent on Caspase, which leads to the production of proinflammatory mediators. Mitochondria also play a crucial role in cell death, with mitochondrial outer membrane permeabilization being a key mechanism. Investigating the roles of mitochondria in pyroptosis can provide new strategies for regulating cell death with potential clinical benefits.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Akande Rouchidane Eyitayo, Mathilde Gonin, Hubert Arokium, Stephen Manon
Summary: BCL-2 family members are key regulators of apoptotic cell death in mammals. Studying their ectopic expression in yeast provides valuable insights into their function and regulation mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Samson Eugin Simon, Usman Ahmed, Syed Muhammad Saad, Ayaz Anwar, Khalid Mohammed Khan, Ee Wern Tan, Kuan Onn Tan
Summary: Chemo-resistant cancer cells can acquire robust growth potential through cell signaling mechanisms. Two bioactive compounds, SMS-IV-20 and SMS-IV-40, have been identified to exhibit elevated cytotoxicity against breast cancer cells and enhance chemo-sensitization. Both compounds interact with the MBR signaling pathway and exert antagonistic actions on BCL-2 and BCL-XL, resulting in the down-regulation of their expression and promotion of mitochondrial Cytochrome C release.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Cell Biology
Constanze Kurschat, Arlena Metz, Susanne Kirschnek, Georg Haecker
Summary: Mitochondrial apoptosis is regulated by Bcl-2-family proteins in hematopoietic cells, with Bim neutralizing Mcl-1 to promote cell survival. Noxa plays an important role in progenitor cells, while Bim's importance increases during differentiation to pro-B cells.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Pooja Patel, Arielys Mendoza, Dexter J. Robichaux, Meng C. Wang, Xander H. T. Wehrens, Jason Karch
Summary: The study reveals that inhibiting Bcl-2 family members decreases mitochondrial calcium retention capacity and increases MPTP opening sensitivity. Additionally, inhibition of each Bcl-2 family member exacerbates both apoptotic and necrotic cell death in vitro. Our findings suggest that there is crosstalk between apoptotic and necrotic cell death pathways influenced by Bax/Bak activation/oligomerization on the outer mitochondrial membrane.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
D. Thomalla, L. Beckmann, C. Grimm, M. Oliverio, L. Meder, C. D. Herling, P. Nieper, T. Feldmann, O. Merkel, E. Lorsy, A. da Palma Guerreiro, J. von Jan, I. Kisis, E. Wasserburger, J. Claasen, E. Faitschuk-Meyer, J. Altmueller, P. Nuernberg, T. -P. Yang, M. Lienhard, R. Herwig, K. -A. Kreuzer, C. P. Pallasch, R. Buettner, S. C. Schaefer, J. Hartley, H. Abken, M. Peifer, H. Kashkar, G. Knittel, B. Eichhorst, R. T. Ullrich, M. Herling, H. C. Reinhardt, M. Hallek, M. R. Schweiger, L. P. Frenzel
Summary: This study explores the role of epigenetic events in venetoclax resistance in aggressive lymphoma and high-risk CLL patients. It identifies methylation of a regulatory CpG island within the PUMA promoter as a mechanism for mediating PUMA downregulation and resistance to venetoclax. The loss of PUMA results in metabolic reprogramming and higher oxidative phosphorylation, resembling the metabolic phenotype associated with venetoclax resistance. Additionally, it highlights the critical role of BAX-mediated apoptosis in drug resistance and provides potential therapeutic targets to overcome venetoclax resistance.
Review
Biochemistry & Molecular Biology
Deeksha Kaloni, Sarah T. Diepstraten, Andreas Strasser, Gemma L. Kelly
Summary: Acquired resistance to cell death is a key characteristic of cancer. The BCL-2 protein family members have important roles in regulating apoptotic cell death. Abnormal expression of pro-survival BCL-2 family proteins or reduction in pro-apoptotic BCL-2 family proteins, both leading to inhibition of apoptosis, are commonly observed in various types of cancer. The critical role of pro-survival and pro-apoptotic BCL-2 family proteins in apoptosis regulation makes them attractive targets for cancer treatment. This review discusses the roles of different pro-survival and pro-apoptotic members of the BCL-2 protein family in normal development and organismal function, as well as how defects in apoptosis control contribute to cancer development and therapy resistance. Lastly, the development of inhibitors targeting pro-survival BCL-2 proteins, known as BH3-mimetic drugs, as novel agents for cancer therapy is discussed.
Article
Biochemistry & Molecular Biology
Zhe Peng, Bernhard Gillissen, Antje Richter, Tobias Sinnberg, Max S. Schlaak, Juergen Eberle
Summary: Targeting MAP kinase pathways through BRAF inhibitors has shown promise in treating BRAF-mutated melanoma. However, this approach is ineffective for BRAF-WT melanoma, and relapse often occurs after initial regression. Inhibiting MAP kinase pathways downstream at ERK1/2 or targeting antiapoptotic Bcl-2 proteins like Mcl-1 may provide alternative strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Alakananda Basu
Summary: The interplay between apoptosis and senescence is crucial in cancer development, and targeting the Bcl-2 family proteins could be a promising strategy for cancer therapy. Therapy-induced senescence (TIS), induced by chemotherapeutic agents, has been controversial in its effect on therapeutic outcome. Clearance of senescent cells and overcoming their pro-survival mechanisms are important challenges in cancer treatment. This review article discusses recent literature on the role of the Bcl-2 family proteins in apoptosis and senescence, and the progress and limitations in targeting them for cancer therapy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Daniel Barriuso, Lucia Alvarez-Frutos, Lucia Gonzalez-Gutierrez, Omar Motino, Guido Kroemer, Roberto Palacios-Ramirez, Laura Senovilla
Summary: The Bcl-2 family of proteins, known for regulating apoptosis, is also involved in cellular senescence. These proteins play a role in determining the entry into senescence and the expression levels are modulated during senescence, promoting cell survival. Manipulation of Bax and Bcl-2 expression affects the appearance and survival of tetraploid cells. Understanding the role of Bcl-2 family proteins in senescence can lead to new therapeutic strategies for targeting cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Elisabetta Valentini, Simona D'Aguanno, Marta Di Martile, Camilla Montesano, Virginia Ferraresi, Alexandros Patsilinakos, Manuela Sabatino, Lorenzo Antonini, Martina Chiacchiarini, Sergio Valente, Antonello Mai, Gianni Colotti, Rino Ragno, Daniela Trisciuoglio, Donatella Del Bufalo
Summary: Bcl-2 family anti-apoptotic proteins play a significant role in cancer, and finding new molecules targeting these proteins has therapeutic potential. Through virtual screening and experimental validation, IS20 and IS21 were identified as compounds that can inhibit the activity of Bcl-2 family proteins and have anti-proliferative and pro-apoptotic effects on various tumors.
Review
Biochemistry & Molecular Biology
Shashank Dadsena, Andreas Jenner, Ana J. Garcia-Saez
Summary: Apoptotic cell death plays a crucial role in development and tissue homeostasis, and MOMP is a central event in this process. Researchers focus on the interaction network of Bcl-2 family proteins and other regulatory elements, emphasizing the importance of single-molecule techniques in uncovering apoptosis regulation mechanisms.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Immunology
Zhenjie Cao, Xin Yang, Tao Li, Zhiru Liu, Pengfei Li, Yongcan Zhou, Yun Sun
Summary: TroBcl2, an anti-apoptotic regulator, was cloned and its role in apoptosis was investigated in this study. It was found that TroBcl2 was widely distributed in various tissues and its expression was upregulated after LPS stimulation. Functional experiments demonstrated that TroBcl2 inhibits apoptosis by reducing mitochondrial membrane potential loss, decreasing DNA fragmentation, preventing cytochrome c release into the cytoplasm, and reducing caspase 3 and caspase 9 activations.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Lisenn Lalier, Francois Vallette, Stephen Manon
Summary: This review examines the role of mitochondrial import machineries in the localization of Bcl-2 family members and how these machineries regulate the function of pro- and anti-apoptotic proteins in resting and apoptotic cells.
Article
Biochemistry & Molecular Biology
Chathura D. Suraweera, Suresh Banjara, Mark G. Hinds, Marc Kvansakul
Summary: The B-cell lymphoma-2 (Bcl-2) family of genes regulates intrinsic apoptosis by coordinating the integrity of the mitochondrial outer membrane. Bcl-2 genes are present in early metazoans and have different variations among species. The structure of Bcl-2 proteins is highly conserved over evolutionary time, and some Bcl-2 proteins may have non-apoptotic functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Giovanni Quarato, Fabien Llambi, Cliff S. Guy, Jaeki Min, Marisa Actis, Huan Sun, Shilpa Narina, Shondra M. Pruett-Miller, Junmin Peng, Zoran Rankovic, Douglas R. Green
Summary: The imbalance of intracellular Ca2+ and mitochondrial Ca2+ overload can lead to mitochondrial inner membrane permeabilization and cell death, which is distinct from Bcl-2 family-regulated mitochondrial outer membrane permeabilization. Cyclosporin A can prevent cell death by inhibiting Ca2+ release from endoplasmic reticulum stores.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Multidisciplinary Sciences
Ao Guo, Hongling Huang, Zhexin Zhu, Mark J. Chen, Hao Shi, Sujing Yuan, Piyush Sharma, Jon P. Connelly, Swantje Liedmann, Yogesh Dhungana, Zhenrui Li, Dalia Haydar, Mao Yang, Helen Beere, Jason T. Yustein, Christopher DeRenzo, Shondra M. Pruett-Miller, Jeremy Chase Crawford, Giedre Krenciute, Charles W. M. Roberts, Hongbo Chi, Douglas R. Green
Summary: This study identifies components of the cBAF complex as negative regulators of T-mem cell generation and provides insights into the asymmetric distribution of cBAF and MYC during the division of activated CD8+ T cells. Manipulation of cBAF early in T cell differentiation has the potential to improve cancer immunotherapy, as demonstrated in a mouse solid tumor model.
Article
Cell Biology
Douglas R. Green
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Article
Cell Biology
Douglas R. Green
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Article
Cell Biology
Douglas R. Green
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Bart Tummers, Douglas R. Green
Summary: Apoptosis and necroptosis, two forms of cell death, play crucial roles in organismal biology and human diseases. While TNF is well-known to induce these processes, cells can also engage in apoptosis and necroptosis through TNF-independent mechanisms, involving the activation of other receptors and proteins such as TLR-3, TLR-4, and ZBP1. RIPK3 is a key regulator of TNF-independent cell death, mediating both apoptosis and necroptosis in response to TLR3/4 and ZBP1 engagement.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Halime Kalkavan, Mark J. Chen, Jeremy C. Crawford, Giovanni Quarato, Patrick Fitzgerald, Stephen W. G. Tait, Colin R. Goding, Douglas R. Green
Summary: Drug-tolerant persister cells can evade apoptosis and have the ability to colonize and metastasize. These cells also show increased sensitivity to ferroptosis. The release of cytochrome c plays a crucial role in the generation of these drug-tolerant persister cells.
Article
Biochemistry & Molecular Biology
Steven Boeynaems, Shasha Chong, Jorg Gsponer, Liam Holt, Dragomir Milovanovic, Diana M. Mitrea, Oliver Mueller-Cajar, Bede Portz, John F. Reilly, Christopher D. Reinkemeier, Benjamin R. Sabari, Serena Sanulli, James Shorter, Emily Sontag, Lucia Strader, Jeanne Stachowiak, Stephanie C. Weber, Michael White, Huaiying Zhang, Markus Zweckstetter, Shana Elbaum-Garfinkle, Richard Kriwacki
Summary: Over the past 15 years, a new scientific field called biomolecular condensates has emerged, focusing on the study of membraneless bodies in cells and their roles in biological processes and disease. These condensates are formed through phase separation and have been found to play crucial roles in various cellular functions and disease pathways. Through a week-long workshop, scientists discussed the key questions and insights in this field, including the applications of condensates in synthetic biology and potential therapeutic targeting.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Editorial Material
Oncology
Hazheen K. Shirnekhi, Bappaditya Chandra, Richard W. Kriwacki
Summary: In a recent study, Wang and colleagues found that many cancer-associated fusion proteins have a similar structural topology, forming aberrant transcriptional condensates through phase separation. They developed a high-throughput screening method to identify a compound that can dissolve these condensates and reverse aberrant gene expression. This work highlights the potential role of fusion protein-driven condensates in oncogenesis and provides proof of principle for identifying compounds that modulate these condensates.
Article
Cell Biology
Douglas R. Green
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)
Article
Biochemical Research Methods
Jesse D. Gelles, Jarvier N. Mohammed, Yiyang Chen, Tara M. Sebastian, Jerry Edward Chipuk
Summary: This study presents a new method, FLAMBE, for monitoring early activation of BAX and demonstrates its reliability and applicability through investigations on a range of BAX modulators. The study reveals that previously considered "dead" BAX mutants are still responsive to activation, filling a gap in previous research.
CELL REPORTS METHODS
(2022)
Meeting Abstract
Immunology
Erin E. West, Simon Freeley, Marcin M. Kaminski, Nicolas S. Merle, Sharon Veenbergen, Duck-Yeon Lee, Lisa St. John-Williams, J. Will Thompson, Douglas R. Green, Sabine Scholl-Buergi, Daniela Karall, Martina Huemer, Claudia Kemper
JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
Swarna Beesetti, Rhea Sumpter, Douglas R. Green
JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
Ao Guo, Hongling Huang, Zhexin Zhu, Mark J. Chen, Hao Shi, Piyush Sharma, Swantje Liedmann, Dalia Haydar, Mao Yang, Helen Beere, Giedre Krenciute, Charles W. M. Roberts, Hongbo Chi, Douglas R. Green
JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Douglas R. Green
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2022)