Cellular responses to DNA damage and other stresses are important determinants of mutagenesis and impact the development of a wide range of human diseases. TP53 is highly mutated in human cancers and plays an essential role in stress responses and cell fate determination. A central dogma of p53 induction after DNA damage has been that the induction results from a transient increase in the half-life of the p53 protein. Our laboratory recently demonstrated that this long-standing paradigm is an incomplete picture of p53 regulation by uncovering a critical role for protein translational regulation in p53 induction after DNA damage. These investigations led to the discovery of a DNA-damage-induced alternative splicing (AS) pathway that affects p53 and other gene products. The damage-induced AS of p53 pre-mRNA generates the beta isoform of p53 (p53β) RNA and protein, which is specifically required for the induction of cellular senescence markers after ionizing irradiation (IR). In an attempt to elucidate the mechanisms behind the differential regulation and apparent functional divergence between full-length (FL) p53 and the p53β isoform (apoptosis versus senescence, respectively), we identified the differential transcriptome and protein interactome between these two proteins that may result from the unique 10-amino-acid tail in p53β protein.
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http://dx.doi.org/10.3390/cancers13020251 | DOI Listing |
mBio
January 2025
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
As a universal language across the bacterial kingdom, the quorum sensing signal autoinducer-2 (AI-2) can coordinate many bacterial group behaviors. However, unknown AI-2 receptors in bacteria may be more than what has been discovered so far, and there are still many unknown functions for this signal waiting to be explored. Here, we have identified a membrane-bound histidine kinase of the pathogenic bacterium , AsrK, as a receptor that specifically detects AI-2 under low boron conditions.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, United Kingdom. (M.W., M.F., R.O., L.S., M.M., C.M.S.).
Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.
Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.
World J Gastrointest Oncol
January 2025
Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China.
Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
: Tumor associated macrophages (TAMs) are critical components in regulating the immune statuses of the tumor microenvironments. Although TAM has been intensively studied, it is unclear how mitochondrial proteins such as AGK regulate the TAMs' function. : We investigated the AGK function in TAMs using macrophage-specific deficient mice with B16 and LLC syngeneic tumor models.
View Article and Find Full Text PDFTheranostics
January 2025
Cancer Research Center, School of Medicine, Xiamen University, Xiamen, 361102, China.
Immunogenic cell death (ICD) offers a promising avenue for the treatment of triple-negative breast cancer (TNBC). However, optimizing immune responses remains a formidable challenge. This study presents the design of RBCm@Pt-CoNi layered double hydroxide (RmPLH), an innovative sonosensitizer for sonodynamic therapy (SDT), aimed at enhancing the efficacy of programmed cell death protein 1 (PD-1) inhibitors by inducing robust ICD responses.
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