Staphylococcal alpha-toxin is an archetypal killer protein that homo-oligomerizes in target cells to create small transmembrane pores. The membrane-perforating beta-barrel motif is a conserved attack element of cytolysins of Gram-positive and Gram-negative bacteria. Following the recognition that nucleated cells can survive membrane permeabilization, a profile of abundant transcripts was obtained in transiently perforated keratinocytes. Several immediate early genes were found to be upregulated, reminiscent of the cellular response to growth factors. Cell cycle analyses revealed doubling of S + G2/M phase cells 26 h post toxin treatment. Determination of cell counts uncovered that after an initial drop, numbers increased to exceed the controls after 2 days. A non-lytic alpha-toxin mutant remained without effect. The alpha-toxin pore is too small to allow egress of cytosolic growth factors, and evidence was instead obtained for growth signalling via the epidermal growth factor receptor (EGFR). Inhibition of the EGFR or of EGFR-proligand-processing blocked the mitogenic effect of alpha-toxin. Western blots with phospho-specific antibodies revealed activation of the EGFR, and of the adapter protein Shc. Immediate early response and proliferation upon transient plasma membrane pore formation by bacterial toxins may represent a novel facet of the complex interaction between pathogen and host.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1462-5822.2006.00733.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
N-Substituted-5- [(2,5-Dihydroxybenzyl)amino]salicylamides as Lavendustin Analogs: Antiproliferative Activity, COMPARE Analyses, Mechanistic, Docking, ADMET and Toxicity Studies.
Chem Biol Drug Des
January 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Target cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors; 5-([2,5-Dihydroxybenzyl]amino)salicylamides (Compounds 1-11) were examined for potential anticancer activity, with a trial to assess the underlying possible mechanisms. Compounds were assessed at a single dose against 60 cancer cell lines panel and those with the highest activity were tested in the five-dose assay. COMPARE analysis was conducted to explore potential mechanisms underlying their biological activity.
View Article and Find Full Text PDFCombination of Carbonic Anhydrase Isoform IX Inhibitors and Gefitinib Suppresses on the Invasive Potential of Non-Small Cell Lung Cancer Cells.
Biochemistry (Mosc)
December 2024
Medicinal Chemistry Center, Togliatti State University, Togliatti, 445020, Russia.
Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions.
View Article and Find Full Text PDFPost-Selection Design of Aptamers: Comparative Study of Affinity of the DNA Aptamers to Recombinant Extracellular Domain of Human Epidermal Growth Factor Receptors.
Biochemistry (Mosc)
December 2024
Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia.
The current work presents comparative assessment of affinity of the designed DNA aptamers for extracellular domain of the human epidermal growth factor receptor (EGFR*). The affinity data of the 20 previously published aptamers are summarized. Diversity of the aptamer selection methods and techniques requires unification of the comparison algorithms, which is also necessary for designing aptamers used in the post-selection fitting to the target EGFR* protein.
View Article and Find Full Text PDF[Effect of SMARCA4 mutations on the outcomes of patients with advanced EGFR mutant lung adenocarcinoma].
Zhonghua Yi Xue Za Zhi
January 2025
Department of Medical Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing210000, China.
To investigate the impact of SMARCA4 mutations on the outcomes of patients with advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. In the Memorial Sloan Kettering Cancer Center (MSK) MetTropism study, 960 patients with advanced EGFR-mutated lung adenocarcinoma were screened and included in the MSK cohort, composing of 313 males and 647 females, with a median [(, )] age of 64 (56, 72) years. A retrospective analysis was conducted on the data of 178 patients with advanced EGFR-mutated lung adenocarcinoma who received EGFR tyrosine kinase inhibitors (TKIs) treatment in the Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, from January 2018 to December 2022.
View Article and Find Full Text PDFDevelopment of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.
Biochem Biophys Res Commun
January 2025
Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki, 852-8521, Japan. Electronic address:
Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur.
View Article and Find Full Text PDFWant 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!