Article
Biochemistry & Molecular Biology
Akande Rouchidane Eyitayo, Axel Boudier-Lemosquet, Stephane Chaignepain, Muriel Priault, Stephen Manon
Summary: The antiapoptotic protein Bcl-xL plays a crucial role in regulating cell death and survival, but many aspects of its functions are still unclear. Using a model system of cell-free protein synthesis and nanodisc insertion, we found that newly synthesized Bcl-xL could spontaneously insert into nanodiscs. The deletion of the C-terminal α-helix of Bcl-xL prevented its insertion into nanodiscs. We also observed that nanodisc insertion protected Bcl-xL from proteolysis and enhanced the insertion of Bax into nanodiscs, similar to what happens in mitochondria. This cell-free synthesis system with nanodiscs provides a suitable platform to study the molecular interactions between Bcl-xL and Bax during their membrane insertion.
Article
Virology
Pin-Han Chen, Tsai-Ching Hsueh, Jen-Leih Wu, Jiann-Ruey Hong
Summary: This study demonstrates that infectious spleen and kidney necrosis virus (ISKNV) infection can induce host cell death through the regulation of mitochondrial membrane potential. The dynamic interaction between pro-apoptotic and anti-apoptotic members of the Bcl-2 family plays a crucial role in this process.
Review
Biochemistry & Molecular Biology
Anna Maria Luciano, Ana B. Perez-Oliva, Victoriano Mulero, Donatella Del Bufalo
Summary: Apoptosis is crucial for eliminating damaged cells in multicellular organisms. Bcl-xL, an anti-apoptotic protein, plays significant roles in cancer, including melanoma, by regulating cell survival, migration, invasion, and angiogenesis. Targeting Bcl-xL may offer potential benefits for cancer patients, but further studies are needed to develop safe and effective inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Jason J. Zoeller, Michael F. Press, Laura M. Selfors, Judy Dering, Dennis J. Slamon, Sara A. Hurvitz, Joan S. Brugge
Summary: The study found upregulation of BCL2 mRNA in patients treated with lapatinib, but in some HER2+/ER- tumors, BCL-2 protein levels were undetectable. Unlike lapatinib, similar BCL-2 upregulation was not observed in patients treated with trastuzumab.
Article
Biochemistry & Molecular Biology
Zihao Mai, Han Sun, Fangfang Yang, Mengyan Du, Xuecheng Cheng, Hongce Chen, Beini Sun, Junlin Wen, Xiaoping Wang, Tongsheng Chen
Summary: Although Bcl-xL can shuttle Bax between mitochondria and cytosol, the mechanism behind the differential regulation of Bax localization by Bcl-xL remains unclear. Bad, a BH3-only protein that interacts with Bcl-xL, is suggested to be crucial for Bcl-xL-mediated Bax translocation.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Paula Hoffmeister-Wittmann, Andreas Mock, Federico Nichetti, Felix Korell, Christop E. Heilig, Anna-Lena Scherr, Michael Gunther, Thomas Albrecht, Eblina Kelmendi, Kaiyu Xu, Luisa Nader, Annika Kessler, Nathalie Schmitt, Sarah Fritzsche, Sofia Weiler, Benjamin Sobol, Albrecht Stenzinger, Stefan Boeck, Christoph B. Westphalen, Klaus Schulze-Osthoff, Jorg Trojan, Thomas Kindler, Wilko Weichert, Karsten Spiekermann, Michael Bitzer, Gunnar Folprecht, Anna-Lena Illert, Melanie Boerries, Frederick Klauschen, Sebastian Ochsenreiter, Jens Siveke, Sebastian Bauer, Hanno Glimm, Benedikt Brors, Jennifer Huellein, Daniel Huebschmann, Sebastian Uhrig, Peter Horak, Simon Kreutzfeld, Jesus M. Banales, Christoph Springfeld, Dirk Jaeger, Peter Schirmacher, Stephanie Roessler, Steffen Ormanns, Benjamin Goeppert, Stefan Froehling, Bruno C. Koehler
Summary: The study identified Bcl-x(L) as a key protein in cell death resistance of CCA and suggested its potential prognostic value, serving as a potential therapeutic target.
LIVER INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Sudjit Luanpitpong, Montira Janan, Juthamas Yosudjai, Jirarat Poohadsuan, Pithi Chanvorachote, Surapol Issaragrisil
Summary: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with poor prognosis due to drug resistance. Overexpression of antiapoptotic Bcl-xL and depletion of proapoptotic Bax contribute to acquired resistance to bortezomib (BTZ) in MCL cells. High Bcl-xL and low Bax levels are associated with poor prognosis in MCL patients. Targeting these proteins using BH3 mimetics and Bax activators may be a promising strategy to overcome drug resistance in MCL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Julie Bas, Trang Nguyen, Germain Gillet
Summary: Bcl-2 family proteins, known for their role in regulating apoptosis, also have non-canonical functions in the CNS. Bcl-xL, a close homolog of Bcl-2, plays a crucial role in neuronal development, promoting ATP generation in mitochondria and contributing to synaptic transmission without causing cell death. Understanding the roles of cell death machinery in neurons may have important clinical implications for degenerative diseases and aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Cristina Mas-Bargues, Consuelo Borras, Jose Vina
Summary: Cellular senescence is related to the inability of cells to adapt to stress conditions, a specific level of senescence can promote development, remodeling and healing, while chronicity of senescence can result from constant stresses and a weakening immune system. Centenarians overexpress Bcl-xL, which helps them avoid the deleterious effects of accumulated senescent cells and maintain a fully functional immune system. There is a paradox in the fact that Bcl-xL inhibitors have been shown to protect from aging in animal models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Kaiming Li, Mark F. van Delft, Grant Dewson
Summary: Apoptotic cell death plays important roles in physiological and pathological processes, especially in cancer therapy and neurodegenerative diseases. Inhibitors of apoptosis have emerged as a potential strategy to combat pathological cell loss, serving as important research tools due to their mechanisms of action, advantages, and limitations.
Article
Biochemistry & Molecular Biology
Qiwen Shi, Bei Hu, Chen Yang, Lan Zhao, Jing Wu, Nan Qi
Summary: Arsenic is a common environmental pollutant that can also be used as a chemotherapeutic agent for acute promyelocytic leukemia. The relationship between arsenic exposure and lung diseases is established, but the molecular mechanisms are poorly understood. Research shows that ATF3 plays a pro-apoptotic role in arsenic-induced airway epithelial apoptosis by transcriptionally regulating DR5 and Bcl-xL, highlighting its potential as an early and sensitive biomarker for arsenic-induced lung injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Parasitology
Shanming Hu, Yanan Wang, Zhengmao Xu, Yongzhi Zhou, Jie Cao, Houshuang Zhang, Jinlin Zhou
Summary: The study found that the transcription levels of the RhBax gene in ticks increase significantly at all developmental stages, while the transcription levels of both RhBcl-2 and RhBax increase more significantly in the female salivary glands. Inhibiting RhBcl-2 expression significantly inhibited tick feeding, while interference with RhBax had no effect on tick feeding.
PARASITES & VECTORS
(2021)
Article
Biochemistry & Molecular Biology
Katherine A. Veleta, Abigail H. Cleveland, Benjamin R. Babcock, You-Wen He, Duhyeong Hwang, Marina Sokolsky-Papkov, Timothy R. Gershon
Summary: The tendency of brain cells to undergo apoptosis varies during neural development, with proliferative neural progenitors showing a low threshold for apoptosis. The conditional deletion of Bcl2l1 in cerebellar granule neuron progenitors (CGNPs) led to severe hypoplasia in mice due to increased apoptosis. Co-deletion of Bax rescued the phenotype, while co-deletion of Mcl-1 enhanced it, suggesting an intricate regulation of apoptosis and proliferation in CGNPs by Bcl-xL and MCL-1.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Violetta Ritter, Franziska Krautter, Diana Klein, Verena Jendrossek, Justine Rudner
Summary: Hypoxia is a major obstacle to successful radiotherapy for solid tumors. Exposure to acute and adaptation to chronic cycling hypoxia alters Bcl-2 family proteins, leading to increased resistance to apoptosis and decreased radiotherapy success. Targeting the Bcl-2 rheostat with ABT-263 shows promise in overcoming radioresistance of cancer cells exposed to hypoxia.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Medicinal
Mike-Andrew Westhoff, Marie Schuler-Ortoli, Daniela Zerrinius, Amina Hadzalic, Andrea Schuster, Hannah Strobel, Angelika Scheuerle, Tiana Wong, Christian Rainer Wirtz, Klaus-Michael Debatin, Aurelia Peraud
Summary: Medulloblastoma is a common solid tumor in children, and current treatments are not highly effective. Modulating the Bcl-2 family members could potentially improve the treatment outcomes by inhibiting tumor cells' resistance to apoptosis.