Activating transcription factor 4 (Atf4), which is modulated by the protein kinase RNA-like ER kinase (PERK), is a stress-induced transcription factor responsible for controlling the expression of a wide range of adaptive genes, enabling cells to withstand stressful conditions. However, the impact of the Atf4 signaling pathway on airway regeneration remains poorly understood. In this study, we used mouse airway epithelial cell culture models to investigate the role of PERK/Atf4 in respiratory tract differentiation. Through pharmacological inhibition and silencing of ATF4, we uncovered the crucial involvement of PERK/Atf4 in the differentiation of basal stem cells, leading to a reduction in the number of secretory cells. ChIP-seq analysis revealed direct binding of ATF4 to regulatory elements of genes associated with osteoblast differentiation and secretory cell function. Our findings provide valuable insights into the role of ATF4 in airway epithelial differentiation and its potential involvement in innate immune responses and cellular adaptation to stress.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766780 | PMC |
| http://dx.doi.org/10.26508/lsa.202302284 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integration of basal and apical embryo lineage regulators controls F-actin cable integrity and zygote asymmetry in .
Proc Natl Acad Sci U S A
January 2025
State Key Laboratory of Wheat Improvement, College of Life Science, Shandong Agricultural University, Tai'an 271018, China.
In many plants, the asymmetric division of the zygote sets up the apical-basal body axis. In the cress , the zygote coexpresses regulators of the apical and basal embryo lineages, the transcription factors WOX2 and WRKY2/WOX8, respectively. WRKY2/WOX8 activity promotes nuclear migration, cellular polarity, and mitotic asymmetry of the zygote, which are hallmarks of axis formation in many plant species.
View Article and Find Full Text PDFChromatin enables precise and scalable gene regulation with factors of limited specificity.
Proc Natl Acad Sci U S A
January 2025
Institute of Science and Technology Austria, AT-3400 Klosterneuburg, Austria.
Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs).
View Article and Find Full Text PDFStructural basis of nearest-neighbor cooperativity in the ring-shaped gene regulatory protein TRAP from protein engineering and cryo-EM.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210.
The homo-dodecameric ring-shaped RNA binding attenuation protein (TRAP) from binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be similar. Proximity between the ligand binding sites, and the ligand-coupled disorder-to-order transition has implicated nearest-neighbor interactions in cooperativity.
View Article and Find Full Text PDFDeep conservation complemented by novelty and innovation in the insect eye ground plan.
Proc Natl Acad Sci U S A
January 2025
Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
A spectacular diversity of forms and features allow species to thrive in different environments, yet some structures remain relatively unchanged. Insect compound eyes are easily recognizable despite dramatic differences in visual abilities across species. It is unknown whether distant insect species use similar or different mechanisms to pattern their eyes or what types of genetic changes produce diversity of form and function.
View Article and Find Full Text PDFANAC044 orchestrates mitochondrial stress signaling to trigger iron-induced stem cell death in root meristems.
Proc Natl Acad Sci U S A
January 2025
Ministry of Education Key Laboratory of Environment Remediation and Ecological Health, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
While iron (Fe) is essential for life and plays important roles for almost all growth related processes, it can trigger cell death in both animals and plants. However, the underlying mechanisms for Fe-induced cell death in plants remain largely unknown. S-nitrosoglutathione reductase (GSNOR) has previously been reported to regulate nitric oxide homeostasis to prevent Fe-induced cell death within root meristems.
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!