BAX is a proapoptotic BCL-2 family member that lies dormant in the cytosol until converted into a killer protein in response to cellular stress. Having recently identified the elusive trigger site for direct BAX activation, we now delineate by NMR and biochemical methods the essential allosteric conformational changes that transform ligand-triggered BAX into a fully activated monomer capable of propagating its own activation. Upon BAX engagement by a triggering BH3 helix, the unstructured loop between α helices 1 and 2 is displaced, the carboxy-terminal helix 9 is mobilized for membrane translocation, and the exposed BAX BH3 domain propagates the death signal through an autoactivating interaction with the trigger site of inactive BAX monomers. Our structure-activity analysis of this seminal apoptotic process reveals pharmacologic opportunities to modulate cell death by interceding at key steps of the BAX activation pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050027 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2010.10.019 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The effect of biosynthesized zinc oxide nanoparticles on gene expression and apoptosis in triple-negative breast cancer cells.
Daru
December 2024
Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Objective(s): Some forms of breast cancer such as triple-negative phenotype, are serious challenge because of high metastatic cases, high mortality and resistance to conventional therapy motivated the search for alternative treatment approaches. Nanomaterials are promising candidates and suitable alternatives for improving tumor and cancer cell treatments.
Materials And Methods: Biosynthesis of ZnO NPs by help of Berberis integerrima fruit extract, has been done.
Integrating UPLC-MS/MS Bioinformatics and In Vivo Experiments Validation to Elucidate the Mechanism of Wenzi Jiedu Decoction in Suppressing Colorectal Cancer.
Phytochem Anal
December 2024
Institute of Oncology, the First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Objectives: We used ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), bioinformatics, and in vivo experiments to study the anti-colorectal cancer (CRC) effects of Wenzi Jiedu Decoction (WJD).
Methods: Detected the main components of WJD by UPLC-MS/MS. Obtained WJD targets and CRC targets through the open source database.
The interaction of isoquinoline alkaloid crebanine with immunoglobulin G and cytotoxic effects toward MCF-7 breast cancer cell line.
Int J Biol Macromol
December 2024
The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. Electronic address:
In this study, the interaction of crebanine, an isoquinoline alkaloid, with immunoglobulin G (IgG) was evaluated. Subsequently, the anticancer effects of crebanine in MCF-7 breast cancer cells were assessed. The results demonstrate that static quenching plays a key role in the fluorescence quenching of the IgG by crebanine, and some embedded hydrophobic patches of the IgG are exposed upon interaction with crebanine, while the characteristic β-sheet conformation of the IgG was almost preserved.
View Article and Find Full Text PDFPlatelet-rich plasma enhances remodeling of combined gastrocnemius muscle and achilles tendon injuries in rat model: Reducing fibrosis, modulating gene (MMP9, Bax, HMGB1, and IGF) expression, and restoring histopathological and ultrastructural changes.
Tissue Cell
December 2024
Department of Anatomy and Embryology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Sheikh, Egypt.
Muscle and tendon injuries are prevalent occurrences during sports activities. Platelet-rich plasma (PRP) is known for its rich content of factors essential for wound healing, inflammation reduction, and tissue repair. Despite its recognized benefits, limited information is available regarding PRP's effectiveness in addressing combined surgical injuries to the gastrocnemius muscle and Achilles tendon.
View Article and Find Full Text PDFLong term effects of gamma radiation on inflammatory and apoptotic biomarkers in nuclear medicine staff.
J Med Imaging Radiat Sci
December 2024
Department of Medical Radiation Engineering, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
Background: Gamma radiation at low doses might have potential health effects in long-term exposure. The current study was aimed to search cell death pathway and inflammatory biomarkers in nuclear medicine workers with long-term exposure to gamma radiation.
Material And Methods: Fifty cases with a history of 10 years' exposure to gamma radiation and 30 normal individuals were included in the current study.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!