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The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge.
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http://dx.doi.org/10.1016/j.jmgm.2016.05.007 | DOI Listing |
Cell Death Dis
December 2024
University of Zürich, Institute of Anatomy, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.
View Article and Find Full Text PDFHemasphere
December 2024
Department of Hematology, University Hospital of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain.
Antiapoptotic Bcl-2 family proteins are involved in myeloma cell survival. To date, their expression in multiple myeloma (MM) patients has mostly been analyzed at the RNA level. In the present study, we quantified for the first time the protein expression of the Bcl2-family members using a capillary electrophoresis immunoassay in 120 newly diagnosed MM patients, aged ≤65 years, treated in the context of the PETHEMA/GEM2012 study.
View Article and Find Full Text PDFCell Death Differ
December 2024
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Senescent cells are commonly detected in tumors after chemo and radiotherapy, leading to a characteristic cellular phenotype that resists apoptotic cell death. In this study, we used multiple melanoma cell lines, molecular markers, and therapies to investigate the key role of the BCL-2 family proteins in the survival of senescent cells. We first used BH3 profiling to assess changes in apoptotic priming upon senescence induction.
View Article and Find Full Text PDFHum Exp Toxicol
November 2024
Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Background: Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers, characterized by the malignant proliferation of leukemic cells. Despite advancements in treatment, the prognosis for refractory and relapsed ALL remains poor, underscoring the need for novel therapeutic targets and approaches.
Methods: To investigate the anti-leukemic properties of MG132, MTS assays were employed to assess cell viability, and flow cytometry was used to evaluate apoptosis.
Food Nutr Res
October 2024
Department of Food Science and Human Nutrition, Jeonbuk National University, Jeonju, Republic of Korea.
There is a significant global increase in colorectal cancer (CRC) among young adults. , one of the signature Korean traditional fermented foods, contains various bioactive compounds and has multiple health-beneficial effects, including anticancer effects; however, the detailed cellular and molecular mechanisms of its anticancer outcomes are not fully understood. The objective of the present study was to investigate the detailed underlying anticancer mechanisms of in CRC cells.
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