In healthy cells the antiapoptotic protein Bcl-2 adopts a topology typical of tail-anchored proteins with only the hydrophobic carboxyl terminus inserted into the membrane, as shown by labeling cell lysates with a membrane-impermeant sulfhydryl-specific reagent. Induction of apoptosis in cells triggered a change in the conformation of Bcl-2 such that cysteine 158 near the base of helix 5 inserted into the lipid bilayer of both endoplasmic reticulum and mitochondria where it was protected from labeling. Addition of a peptide corresponding to the BH3 domain of the proapoptotic protein Bim to cell lysates triggered a similar conformational change in Bcl-2, demonstrating that preexisting, membrane-bound Bcl-2 proteins change topology.
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http://dx.doi.org/10.1016/s1097-2765(04)00263-1 | DOI Listing |
Am J Respir Cell Mol Biol
January 2025
Wayne State University, Division of Pulmonary, Critical Care and Sleep Medicine, Detroit, Michigan, United States;
Numerous chronic human disorders are associated with immune activation by obscure antigen(s). We identified a novel sarcoidosis-epitope (ChainA) by immunoscreening of a novel T7 phage library and confirmed an abundance of ChainA IgG-antibody in sarcoidosis. We tested whether ChainA epitope elicits immune responses through B-cell activation, plasma cell differentiation and antibody production.
View Article and Find Full Text PDFACS Appl Bio Mater
January 2025
Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat 382355, India.
Golgi apparatus (GA) and endoplasmic reticulum (ER) are two of the interesting subcellular organelles that are critical for protein synthesis, folding, processing, post-translational modifications, and secretion. Consequently, dysregulation in GA and ER and cross-talk between them are implicated in numerous diseases including cancer. As a result, simultaneous visualization of the GA and ER in cancer cells is extremely crucial for developing cancer therapeutics.
View Article and Find Full Text PDFiScience
January 2025
Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Québec H7V 1B7, Canada.
During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles.
View Article and Find Full Text PDFFront Pharmacol
January 2025
The Third Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.
Background: The Beclin-1/Bcl-2 complex plays a pivotal role in regulating both autophagy and apoptosis in osteoblasts affected by osteoporosis. This study first investigates whether the Bushen Jianpi Huoxue Formula can enhance the cellular function of osteoblasts. Additionally, it initially explores the functional mechanism of Beclin-1/Bcl-2-related apoptosis.
View Article and Find Full Text PDFFront Microbiol
January 2025
Department of Microbiology, Faculty of Medicine, Shimane University, Izumo, Japan.
Current treatments for hepatitis B virus (HBV), such as interferons and nucleic acid analogs, have limitations due to side effects like depression and the development of drug-resistant mutants, highlighting the need for new therapeutic approaches. In this study, we identified microRNA-3145 (miR-3145) as a host-derived miRNA with antiviral activity that is upregulated in primary hepatocytes during HBV infection. The expression of its precursor, pri-miR-3145, increased in response to the the virus infection, and miR-3145 downregulated the hepatitis B virus S (HBS) antigen and hepatitis B virus X (HBX), thereby inhibiting viral replication.
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