G protein-coupled receptors (GPCRs) are a diverse family of cell surface receptors implicated in various physiological functions, making them common targets for approved drugs. Many GPCRs are abnormally activated in cancers and have emerged as therapeutic targets for cancer. Neuropeptide FF receptor 2 (NPFFR2) is a GPCR that helps regulate pain and modulates the opioid system; however, its function remains unknown in cancers.
View Article and Find Full Text PDFThe pathogenic fungus Cryptococcus neoformans must overcome iron limitation to cause disease in mammalian hosts. Previously, we reported a screen for insertion mutants with poor growth on haem as the sole iron source. In this study, we characterised one such mutant and found that the defective gene encoded a Vam6/Vps39/TRAP1 domain-containing protein required for robust growth on haem, an important iron source in host tissue.
View Article and Find Full Text PDFMonothiol glutaredoxins are important regulators of iron homeostasis that play conserved roles in the sensing and trafficking of iron-sulfur clusters. We previously characterized the role of the monothiol glutaredoxin Grx4 in iron homeostasis, the interaction with the iron regulator Cir1, and virulence in Cryptococcus neoformans. This important fungal pathogen causes cryptococcal meningoencephalitis in immunocompromised individuals worldwide.
View Article and Find Full Text PDFFront Cell Infect Microbiol
June 2020
The Mkt1-Pbp1 complex promotes mating-type switching by regulating the translation of mRNA in . Here, we performed immunoprecipitation assays and mass spectrometry analyses in the human fungal pathogen to show that Pbp1, a poly(A)-binding protein-binding protein, interacts with Mkt1 containing a PIN like-domain. Association of Pbp1 with Mkt1 was confirmed by co-immunoprecipitation assays.
View Article and Find Full Text PDFFungal development is regulated by a variety of transcription factors in Aspergillus nidulans. Previous studies demonstrated that the NF-κB type velvet transcription factors regulate certain target genes that govern fungal differentiation and cellular metabolism. In this study, we characterize one of the VosA/VelB-inhibited developmental genes called vidA, which is predicted to encode a 581-amino acid protein with a CH zinc finger domain at the C-terminus.
View Article and Find Full Text PDFCluh is a cytosolic protein that is known to specifically bind the mRNAs of nuclear-encoded mitochondrial proteins and play critical roles in mitochondrial biogenesis. Here, we report the role of Cluh in adipogenesis. Our study shows that mRNA expression of Cluh is stimulated during adipogenesis, and that cAMP/Creb signalling increases its transcription.
View Article and Find Full Text PDFDietary fiber is a group of important food polysaccharides, which may improve gastrointestinal function and alter the bioavailability and nutritional value of other food components. The interaction mechanism of psyllium fiber (PSY) and whey protein (WP) and the influence on the characteristics of polysaccharides and protein were investigated. The results of circular dichroism spectra and differential scanning calorimetry analysis showed that PSY could protect WP by increasing its melting temperature.
View Article and Find Full Text PDFMon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Mon1, in a human fungal pathogen, . Mutation in resulted in hypersensitivity to thermal stress.
View Article and Find Full Text PDFCalcineurin modulates environmental stress survival and virulence of the human fungal pathogen Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets including Crz1, Pbp1, and Puf4 in In this study, we characterized Had1, which is one of the putative calcineurin substrates belonging to the ubiquitously conserved haloacid dehalogenase β-phosphoglucomutase protein superfamily. Growth of the ∆ mutant was found to be compromised at 38° or higher. In addition, the ∆ mutant exhibited increased sensitivity to cell wall perturbing agents, including Congo Red and Calcofluor White, and to an endoplasmic reticulum stress inducer dithiothreitol.
View Article and Find Full Text PDFPeripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring in the extraosseous region. The present report describes a spontaneous tumor in male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right mandibular region was first observed when the rat was 42 weeks and remained until the terminal sacrifice date when the animal was 48 weeks of age.
View Article and Find Full Text PDFGerm line-specific genes are activated in somatic cells during tumorigenesis, and are accordingly referred to as cancer germline genes. Such genes that act on piRNA (Piwi-interacting RNA) processing play an important role in the progression of cancer cells. Here, we show that the spermatogenic transposon silencer maelstrom (Mael), a piRNA-processing factor, is required for malignant transformation and survival of cancer cells.
View Article and Find Full Text PDFMad2, a key component of the spindle checkpoint, is closely associated with chromosomal instability and poor prognosis in cancer. p31comet is a Mad2-interacting protein that serves as a spindle checkpoint silencer at mitosis. In this study, we showed that p31comet-induced apoptosis and senescence occur via counteraction of Mad2 activity.
View Article and Find Full Text PDFThe iron uptake and utilization pathways play a critical role in allowing human pathogens, including Cryptococcus neoformans, the causative agent of fatal meningoencephalitis, to survive within the mammalian body by competing with the host for iron. Here we show that the iron regulon is also required for diverse environmental stress responses and that in C. neoformans, it is regulated by the high-osmolarity glycerol response (HOG) pathway.
View Article and Find Full Text PDFSpontaneous multiple granulomas were present in the animal under the SPF condition and without chemical treatment, in a 19-week-old male Sprague-Dawley control-group rat. Here we describe multiple granulomas and prominent diffuse infiltration by eosinophils in the cecal submucosa, and arteritis in the mesenteric arteries. The multiple granulomas were characterized by central eosinophilic degeneration or necrosis, prominent eosinophils, many multi-nucleated giant cells and abundant fibroblasts.
View Article and Find Full Text PDFThe basidiomycete fungus Cryptococcus neoformans infects humans via inhalation of desiccated yeast cells or spores from the environment. In the absence of effective immune containment, the initial pulmonary infection often spreads to the central nervous system to result in meningoencephalitis. The fungus must therefore make the transition from the environment to different mammalian niches that include the intracellular locale of phagocytic cells and extracellular sites in the lung, bloodstream, and central nervous system.
View Article and Find Full Text PDFPreviously, we have shown that PDE2 is required for hyphal development and cell wall integrity in Candida albicans. In the present study, we have investigated the effects of its deletion by genome-wide transcriptome profiling. Changes in expression levels of genes involved in metabolism, transcription, protein and nucleic acids synthesis, as well as stress responses, cell wall and membrane biogenesis, adherence and virulence have been observed.
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