DIF-1 (differentiation-inducing factor1) is a polyketide produced by Dictyostelium prespore cells which induces initially uncommitted cells to differentiate as prestalk cells. Exposure of cells to DIF-1 causes transitory hypo-phosphorylation of seven serine residues in YelA, a protein with a region of strong homology to the MIF4G domain of the eukaryotic initiation factor eIF4G. Based upon its domain architecture, which in one important aspect closely resembles that of Death-Associated Protein 5 (DAP5), we predict a role in stimulating internal ribosome entry-driven mRNA translation. The two paradigmatic DIF-1 inducible genes are ecmA (extracellular matrixA) and ecmB. In support of a YelA function in DIF-1 signaling, a YelA null strain showed greatly increased expression of ecmA and ecmB in response to DIF-1. Also, during normal development in the null strain, expression of the two genes is accelerated. This is particularly evident for ecmB, a marker of stalk tube and supporting structure differentiation. Mutants in DIF-1 bio-synthesis or signaling display a rudimentary or no basal disc and, conversely, YelA null mutants produce fruiting bodies with a highly enlarged basal disc that ectopically expresses a stalk tube-specific marker. Thus YelA acts as an antagonist of DIF-1 signaling, with a consequent effect on cell type proportioning and it is predicted to act as a translational regulator.
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Eur J Pharmacol
January 2025
Department of Pharmacology, Faculty of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan. Electronic address:
We previously reported differentiation-inducing factor-1 (DIF-1) activated glycogen synthase kinase-3 (GSK-3) in various mammalian cells. GSK-3 has been proposed to regulate a number of signaling pathway including TAZ/YAP signaling pathway. To clarify the effect of DIF-1 on TAZ/YAP signaling pathway, we examined whether DIF-1 affect the expression levels of TAZ and YAP.
View Article and Find Full Text PDFOpen Res Eur
December 2024
School of Life Sciences, University of Dundee School of Life Sciences, Dundee, Scotland, DD15EH, UK.
Background: Dictyostelia are soil amoebas that aggregate to form fruiting bodies with spores and stalk cells in response to starvation. Where known, species across the dictyostelid phylogeny use secreted cAMP, detected by cAMP receptors (cARs) to induce the differentiation of spores and to organize fruiting body construction. However, recent deletion of the single of ) left both its fruiting bodies and spores intact.
View Article and Find Full Text PDFInt J Biol Macromol
November 2024
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China; National Key Laboratory of Green Pesticide, College of Plant Protection, South China Agricultural University, Guangzhou 510642, China. Electronic address:
Drosophila NF-κB transcription factor Dif has been well known for its function in innate immunity, and recent study also reveals its role in neuronal cells. However, the underlying mechanisms of Dif in the brain remain elusive. In this study, we aim to investigate the function of Dif in Drosophila brain development and how Dif regulates structure and plasticity of the brain to affect aging and behaviors.
View Article and Find Full Text PDFLife Sci
August 2024
Department of Pharmacology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:
J Pharmacol Sci
March 2024
Department of Vascular Biology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan. Electronic address:
For the treatment and prevention of autoinflammatory diseases, it is essential to develop the drug, regulating the innate immune system. Although differentiation-inducing factor (DIF) derivatives, extracted from the cellular slime mold, Dictyostelium discoideum, exhibit immunomodulatory effects, their effects on the regulation of innate immunity in brain are unknown. In this study, we used the human cerebral microvascular endothelial cell line, hCMEC/D3, to investigate the effects of DIF derivatives on the generation of C-X-C motif chemokine (CXCL) 10 and interferon (IFN)-β induced by polyinosinic-polycytidylic acid (poly IC).
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