The p53 tumor suppressor is a multifaceted polypeptide that impedes tumorigenesis by regulating a diverse array of cellular processes. Triggered by a wide variety of stress stimuli, p53 transcriptionally regulates genes involved in the canonical tumor suppression pathways of apoptosis, cell-cycle arrest, and senescence. We recently discovered a novel mechanism whereby p53 inhibits cystine uptake through repression of the SLC7A11 gene to mediate ferroptosis. Importantly, this p53-SLC7A11 axis is preserved in the p53(3KR) mutant, and contributes to its ability to suppress tumorigenesis in the absence of the classical tumor suppression mechanisms. Here, we report that wild type p53 can induce both apoptosis and ferroptosis upon reactive oxygen species (ROS)-induced stress. Furthermore, we demonstrate that p53's functional N-terminal domain is required for its capacity to regulate oxidative stress responses and ferroptosis. Notably, activated p53 dynamically modulates intracellular ROS, causing an initial reduction and a subsequent increase of ROS levels. Taken together, these data implicate ferroptosis as an additional component of the cell death program induced by wild type p53 in human cancer cells, and reveal a complex and dynamic role of p53 in oxidative stress responses.
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http://dx.doi.org/10.1080/15384101.2015.1068479 | DOI Listing |
Brain Struct Funct
January 2025
Applied Psychology, Faculty of Education, University of Western Ontario, 1137 Western Rd, London, ON, N6G 1G7, Canada.
Children and adolescents with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) may be more susceptible to early life stress compared to their neurotypical peers. This increased susceptibility may be linked to regionally-specific changes in the striatum and amygdala, brain regions sensitive to stress and critical for shaping maladaptive behavioural responses. This study examined early life stress and its impact on striatal and amygdala development in 62 children and adolescents (35 males, mean age = 10.
View Article and Find Full Text PDFPlant Physiol
January 2025
The State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing 210095, China.
Chromatin remodeling plays a crucial role in controlling gene transcription by modifying chromatin structure. However, the involvement of chromatin remodeling in plant stress responses, especially cold tolerance, through chromatin accessibility remains largely unexplored. Here, we report that rice (Oryza sativa L.
View Article and Find Full Text PDFPlant Physiol
January 2025
Institute of Biology, University of Graz, Graz, Austria.
Understanding the molecular mechanisms of abiotic stress responses in plants is instrumental for the development of climate-resilient crops. Key factors in abiotic stress responses, such as the proton- pumping pyrophosphatase (AVP1), have been identified, but their function and regulation remain elusive. Here, we explored the post-translational regulation of AVP1 by the ubiquitin-conjugating enzyme UBC34 and its relevance in the salt stress and phosphate starvation responses of Arabidopsis (Arabidopsis thaliana).
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
Key Laboratory of Agricultural Biosafety and Green Production of Upper Yangtze River (Ministry of Education), College of Plant Protection, Southwest University, Chongqing 400715, China.
The mitochondrial voltage-dependent anion channel (VDAC) is the major channel in the mitochondrial outer membrane for metabolites and ions. VDACs also regulate a variety of biological processes, which vary in the number of VDAC isoforms across different eukaryotes. However, little is known about VDAC-mediated biocontrol traits in biocontrol fungi.
View Article and Find Full Text PDFGenes Dev
December 2024
Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19146, USA;
The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.
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