Article
Biochemistry & Molecular Biology
Haolan Wang, Ming Guo, Hudie Wei, Yongheng Chen
Summary: The apoptotic pathway is regulated by protein-protein interactions within the Bcl-2 family. The BH3 peptide derived from the BH3-only protein Bmf binds with high affinity to pro-survival proteins Bcl-2 and Bcl-xL, but has a lower affinity for Mcl-1. The study provides structural insights into the specificity and interaction mechanism of Bmf BH3 binding to pro-survival Bcl-2 family proteins.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
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
Multidisciplinary Sciences
Joachim Lauterwasser, Franziska Fimm-Todt, Aline Oelgeklaus, Annabell Schreiner, Kathrin Funk, Hugo Falquez-Medina, Ramona Klesse, Guenther Jahreis, Ralf M. Zerbes, Katelyn O'Neil, Martin van der Laan, Xu Luo, Frank Edlich
Summary: This study reveals that hexokinase 1 and hexokinase 2 inhibit apoptotic activator truncated BID, as well as effectors BAX and BAK, by retrotranslocation from mitochondria to cytosol. Mitochondrial hexokinase localization and interactions with BH3 motifs of BCL-2 proteins are essential for the protection against TRAIL- and FasL-induced cell death, independent of glucose phosphorylation. Hexokinase-dependent retrotranslocation of truncated BID serves as a selective protective mechanism against death receptor-induced apoptosis on the mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Walter Douglas Fairlie, Erinna F. Lee
Summary: BCL-2, c-MYC and related proteins play crucial roles in normal cell functioning and are central to various cancers. Genetic lesions leading to deregulation of these proteins contribute to tumor development and survival depending on the cooperation between these protein families.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
Biochemistry & Molecular Biology
Hector Flores-Romero, Lisa Hohorst, Malina John, Marie-Christine Albert, Louise E. King, Laura Beckmann, Tamas Szabo, Vanessa Hertlein, Xu Luo, Andreas Villunger, Lukas P. Frenzel, Hamid Kashkar, Ana J. Garcia-Saez
Summary: This study reveals a previously unrecognized activity of tBID in mediating mitochondrial permeabilization independently of BAX and BAK, which has physiological relevance in immune response and cancer therapy. This novel function of tBID is dependent on a specific helix structure and can be blocked by anti-apoptotic proteins, providing potential implications for therapeutic intervention in bacterial infections and cancer treatment.
Review
Biochemistry & Molecular Biology
Surinder M. Soond, Maria V. Kozhevnikova, Lyudmila V. Savvateeva, Paul A. Townsend, Andrey A. Zamyatnin
Summary: With the increasing importance of cathepsin-mediated substrate proteolysis in tumor biology, the emphasis on therapeutic design and development is growing. In order to target this interaction with tangible therapeutics, consideration must be given to the selectivity of anti- and pro-apoptotic signaling intermediates as downstream substrates for certain activated cathepsin proteases. Further exploration of 'BH3-mimetics' in modulating the relationship between these intermediates and their upstream cathepsin protease regulators is essential for improved therapeutic design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Louise E. King, Ricardo Rodriguez-Enriquez, Robert Pedley, Charlotte E. L. Mellor, Pengbo Wang, Egor Zindy, Michael R. H. White, Keith Brennan, Andrew P. Gilmore
Summary: Mitochondrial priming, an important process in regulating cell apoptosis, is closely related to the retrotranslocation dynamics of Bcl-XL. This study reveals that the binding of Bcl-XL to its BH3-only partners inhibits its retrotranslocation, leading to accumulation of protein complexes carrying priming on mitochondria. Additionally, heterogeneity in priming between cells within a population is found, which predicts their subsequent response to pro-apoptotic signals.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Shani Ben-Zichri, Ravit Malishev, Ofek Oren, Daniel N. Bloch, Ran Taube, Niv Papo, Raz Jelinek
Summary: The study shows that BID, PUMA, and NOXA have significant and divergent effects on the aggregation, cytotoxicity, and membrane interactions of Afi42. Specifically, BID and PUMA accelerate aggregation, reduce toxicity and mitochondrial dysfunction, and inhibit membrane interactions of Afi42, while NOXA exhibits opposite effects. These findings suggest a potential link between the effects of these proapoptotic peptides on Afi42 and the pathophysiological features of AD.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Michael J. Roy, Amelia Vom, Toru Okamoto, Brian J. Smith, Richard W. Birkinshaw, Hong Yang, Houda Abdo, Christine A. White, David Segal, David C. S. Huang, Jonathan B. Baell, Peter M. Colman, Peter E. Czabotar, Guillaume Lessene
Summary: The BCL-2 family of proteins is an important target for anticancer drug development, with inhibitors like ABT-199/vebetoclax showing transformative effects. Developing new validated chemical series for BCL-X-L is desirable.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Surein Arulananda, Erinna F. Lee, W. Douglas Fairlie, Thomas John
Summary: With limited therapeutic options for malignant pleural mesothelioma (MPM), the over-expression of pro-survival BCL-2 family proteins has been identified as a potential mechanism for cell survival in MPM. BH3-mimetics targeting these proteins show promise as a novel treatment option, especially considering the lack of actionable oncogene driver mutations and limited benefit from immune checkpoint inhibition in MPM.
EXPERT REVIEW OF ANTICANCER THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Zhe Zhi, Zhenlin Ouyang, Yibo Ren, Ying Cheng, Peijun Liu, Yurong Wen, Yongping Shao
Summary: This study uncovered a new regulatory mechanism of Bmf activity during anoikis and provided a structural basis for Bmf cytoskeleton tethering and dissociation. The activation of p38 MAPK directly phosphorylated Bmf at multiple sites, including T72, which blocked the interaction between Bmf and DLC2. Additionally, a phosphomimetic mutation of T72 was found to enhance Bmf apoptotic activity in vitro and in a knock-in mouse model.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Oncology
Anna Kawiak, Anna Kostecka
Summary: Breast cancer is the leading cause of cancer-related deaths in women, with estrogen receptor-positive breast cancer accounting for two-thirds of cases. Endocrine therapy has shown benefits in treating estrogen receptor-positive breast cancer, but resistance to therapy remains a challenge. The Bcl-2 family of proteins plays a crucial role in regulating cell survival or death, particularly in resistance to endocrine therapy. Advances have been made in targeting the Bcl-2 family proteins, and their application in estrogen receptor-positive breast cancer has been explored.
Article
Hematology
Donia M. Moujalled, Fiona C. Brown, Chong Chyn Chua, Michael A. Dengler, Giovanna Pomilio, Natasha S. Anstee, Veronique Litalien, Ella Thompson, Thomas Morley, Sarah MacRaild, Ing S. Tiong, Rhiannon Morris, Karen Dun, Adrian Zordan, Jaynish Shah, Sebastien Banquet, Ensar Halilovic, Erick Morris, Marco J. Herold, Guillaum Lessene, Jerry M. Adams, David C. S. Huang, Andrew W. Roberts, Piers Blombery, Andrew H. Wei
Summary: Randomized trials have shown that the combination of the BCL-2 inhibitor venetoclax with azacitidine improves survival in older AML patients, and ongoing clinical trials are testing venetoclax in combination with intensive chemotherapy in fitter patients. However, a significant number of patients still relapse, highlighting the need for a better understanding of relapse mechanisms.
Review
Biochemistry & Molecular Biology
Bonsu Ku
Summary: Anti-apoptotic and anti-autophagic Bcl-2 homologues commonly have a hydrophobic groove that accommodates the BH3 domain. Although the BH3 domain is typically associated with Bcl-2 family members, it has also been found in various non-Bcl-2 family proteins. The author conducted a structural analysis of Bcl-xL complexed with the BH3 domains of four non-Bcl-2 family proteins and suggests that there may be more undiscovered BH3 domain-containing proteins that can control apoptosis, autophagy, or other biological processes.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Prafull Kumar Singh, Aristomenis Roukounakis, Arnim Weber, Kushal Kumar Das, Benedicte Sohm, Andreas Villunger, Ana J. Garcia-Saez, Georg Haecker
CELL DEATH AND DIFFERENTIATION
(2020)
Article
Environmental Sciences
Didier Techer, Nicolas Grosjean, Benedicte Sohm, Damien Blaudez, Marie Le Jean
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2020)
Article
Multidisciplinary Sciences
Michael Keith Kullmann, Silvio Roland Podmirseg, Martina Roilo, Ludger Hengst
SCIENTIFIC REPORTS
(2020)
Article
Cell Biology
Sophia Wedel, Ines Martic, Nina Hrapovic, Susanne Fabre, Corina T. Madreiter-Sokolowski, Thomas Haller, Gerhard Pierer, Christian Ploner, Pidder Jansen-Duerr, Maria Cavinato
MECHANISMS OF AGEING AND DEVELOPMENT
(2020)
Article
Biochemistry & Molecular Biology
Martin Puhr, Andrea Eigentler, Florian Handle, Hubert Hackl, Christian Ploner, Isabel Heidegger, Georg Schaefer, Maximilian P. Brandt, Julia Hoefer, Gabri Van der Pluijm, Helmut Klocker
Summary: The glucocorticoid receptor (GR) plays a critical role in prostate cancer therapy, and finding a targeted approach is crucial. MAO-A has been identified as a direct target of glucocorticoids, playing a significant role in prostate cancer progression. Pharmacological inhibition of MAO-A can impair cell growth in various conditions, offering an innovative therapeutic strategy to overcome therapy resistance.
Article
Cell & Tissue Engineering
Christian Ploner, Tina Rauchenwald, Catherine E. Connolly, Karin Joehrer, Johannes Rainer, Christof Seifarth, Martin Hermann, Markus Nagl, Susanne Lobenwein, Doris Wilflingseder, Giuseppe Cappellano, Evi M. Morandi, Gerhard Pierer
Summary: The presence of adipocytes in wound tissue indicates a prevailing anti-inflammatory environment that can be promoted by NCT treatment, and may be associated with improved healing outcomes.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell Biology
Michael Keith Kullmann, Fragka Pegka, Christian Ploner, Ludger Hengst
Summary: In addition to serving as a CDK inhibitor and tumor suppressor, p57 may also promote tumor growth by activating the proto-oncoprotein c-Jun.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Christophe Pagnout, Angelina Razafitianamaharavo, Benedicte Sohm, Celine Caillet, Audrey Beaussart, Eva Delatour, Isabelle Bihannic, Marc Offroy, Jerome F. L. Duval
Summary: This study investigates the response of lipopolysaccharide-truncated Escherichia coli mutants to TiO2 nanoparticles, showing that different lipopolysaccharide surface phenotypes can affect bacterial sensitivity to the nanoparticles. TiO2 nanoparticles strip the cell membrane, leading to osmotic stress, oxidative stress, and the formation of membrane vesicles, which can act as electrostatic baits for the nanoparticles, highlighting an antagonistic bacterial response to nanoparticle toxicity.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Heidelinde Jaekel, Martin Taschler, Karin Jung, Christina Weinl, Fragka Pegka, Michael Keith Kullmann, Silvio Roland Podmirseg, Sayantanee Dutta, Markus Moser, Ludger Hengst
Summary: The study reveals the importance of p27 tyrosine phosphorylation in v-ABL and BCR::ABL1(p190)-induced transformation. Surprisingly, p27-Y88F mice are more susceptible to v-ABL-induced leukemia/lymphoma, possibly due to a robust reduction of p27-Y88F levels leading to enhanced cell proliferation and accelerated leukemia progression.
Article
Engineering, Biomedical
Daniel Nothdurfter, Christian Ploner, Debora C. Coraca-Huber, Doris Wilflingseder, Thomas Mueller, Martin Hermann, Judith Hagenbuchner, Michael J. Ausserlechner
Summary: This paper presents a novel 3D printed neuroblastoma-tumor-environment model and a biofabrication platform suitable for studying tumor angiogenesis and metastasis.
Article
Cell Biology
Sophia Wedel, Ines Martic, Lena Guerrero Navarro, Christian Ploner, Gerhard Pierer, Pidder Jansen-Duerr, Maria Cavinato
Summary: Knocking down GDF15 expression leads to mitochondrial dysfunction and premature senescence, while the loss of GDF15 in a human skin model causes thinning of the epidermis, a hallmark of skin aging.
Article
Biochemistry & Molecular Biology
Rodrigue S. Yedji, Benedicte Sohm, Virginie Salnot, Francois Guillonneau, Carole Cossu-Leguille, Eric Battaglia
Summary: This study comprehensively investigates and identifies active SHs in zebrafish larvae, identifies SH type biomarkers after exposure to DBP, and determines the overexpressed SHs. The results suggest that targeted proteomics approaches, such as ABPP, can be valuable tools for understanding the mechanism of action related to xenobiotics in ecotoxicology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Jerome F. L. Duval, Angelina Razafitianamaharavo, Isabelle Bihannic, Marc Offroy, Nicolas Lesniewska, Benedicte Sohm, Helene Le Cordier, Christian Mustin, Christophe Pagnout, Audrey Beaussart
Summary: The variation of cell-wall ultrastructure, composition, and nanomechanics of Chlorella vulgaris upon culture ageing and lysozyme treatment was investigated using a combination of atomic force microscopy (AFM) and confocal microscopy. The presence of a fibrillated mesh at the surface of cells harvested in the stationary phase was observed through AFM imaging. The structured network formed by fibrils containing the N-acetyl-D-glucosamine unit was severely damaged by lysozyme treatment. Furthermore, lysozyme was found to affect algal physiology, triggering oxidative stress and changes in cell lipid content.
ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
(2023)
Article
Endocrinology & Metabolism
Markus Mandl, Heike Ritthammer, Asim Ejaz, Sonja A. Wagner, Florian M. Hatzmann, Saphira Baumgarten, Hans P. Viertler, Marit E. Zwierzina, Monika Mattesich, Valerie Schiller, Tina Rauchenwald, Christian Ploner, Petra Waldegger, Gerhard Pierer, Werner Zwerschke