• Korean Journal of Microbiology
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• v.45 no.4
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• pp.312-317
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• 2009

Genome analysis of a model filamentous fungus, Aspergillus nidulans, revealed that there are six putative forkhead genes. Among them, fkhF (AN8949.2) showed A. nidulans-specific. fkhF gene is located in chromosome VII and composed of 2,337 bp coding region for 778 amino acid. Since little is known about the involvement of the forkhead proteins in the developmental process of the filamentous fungi, including A. nidulans, we generated a deletion mutant of fkhF gene and analyzed. Deletion of fkhF resulted in less-dense conidiophore formation in a solid culture. However, the sexual developmental process or cleistothecia formation was normal. Furthermore, fkhF deletion mutant produced conidiophores and conidia under the submerged culture, suggesting that the fkhF gene is involved in repression of inappropriated induction and maturation of asexual developmental process but not in sexual development.

• The Korean Journal of Mycology
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• v.38 no.2
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• pp.160-166
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• 2010

A homothallic filamentous fungus Aspergillus nidulans has been used as the a model organism for studying growth and development for eukaryotic system. Various studies about specific transcription factors have been performed for elucidating the molecular mechanisms of growth, asexual and sexual developmental processes. Among them, the fkhE gene (AN2025.3) is located in chromosome VII and contains an ORF encoding 718 amino acid polypeptide intervening with two short introns. The cDNA sequencing revealed that at least four types of alternative splicing events were occurred when the fkhE gene was transcribed. The putative FkhE polypeptide contains a conserved forkhead domain and a bipartite nuclear localization signal at it's N-terminus and C-terminus, respectively. Deletion of fkhE resulted in impaired conidiophore formation in a solid medium. However, the sexual developmental process or cleistothecia formation was normal. Furthermore, fkhE deletion mutant produced conidiophores and conidia under the submerged culture, indicating that the fkhE gene is involved in asexual developmental process similar to the fkhF gene.

• Journal of Microbiology and Biotechnology
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• v.33 no.11
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• pp.1420-1427
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• 2023

The forkhead domain genes are important for development and morphogenesis in fungi. Six forkhead genes fkhA-fkhF have been found in the genome of the model filamentous Ascomycete Aspergillus nidulans. To identify the fkh gene(s) associated with fungal development, we examined mRNA levels of these six genes and found that the level of fkhB and fkhD mRNA was significantly elevated during asexual development and in conidia. To investigate the roles of FkhB and FkhD, we generated fkhB and fkhD deletion mutants and complemented strains and investigated their phenotypes. The deletion of fkhB, but not fkhD, affected fungal growth and both sexual and asexual development. The fkhB deletion mutant exhibited decreased colony size with distinctly pigmented (reddish) asexual spores and a significantly lower number of conidia compared with these features in the wild type (WT), although the level of sterigmatocystin was unaffected by the absence of fkhB. Furthermore, the fkhB deletion mutant produced sexual fruiting bodies (cleistothecia) smaller than those of WT, implying that the fkhB gene is involved in both asexual and sexual development. In addition, fkhB deletion reduced fungal tolerance to heat stress and decreased trehalose accumulation in conidia. Overall, these results suggest that fkhB plays a key role in proper fungal growth, development, and conidial stress tolerance in A. nidulans.

• 한국균학회소식:학술대회논문집
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• 2014.05a
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• pp.39-39
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• 2014

In a homothallic filamentous fungus Aspergillus nidulans, sexual and asexual developments are largely affected by the genetic and environmental factors. To regulate the complex subsets of genes involved in the developmental processes accurately, tight regulations of transcription factors are required. The forkhead type transcription factors are the class of regulators that function in a broad spectrum of cellular and developmental processes in many species from yeast to human. Here, we identified the fkhA and fkhB genes that encode a conserved forkhead transcription factors. The fkhA deletion resulted in the complete loss of fruiting body formation under all conditions favoring sexual development, suggesting that the fkhA gene is required for sexual development in A. nidulans. Overexpression of fkhA resulted in enhanced formation of fruiting bodies under induction condition not only in the normal condition but also in the condition of presence of 0.6 M KCl, which strongly inhibits sexual development. To know the function of the fkhB gene, we also generated fkhB knock-out strain in A. nidulans. Deletion of fkhB resulted in abnormal conidiophore formation under standard conditions and delayed sexual development process, suggesting that the fkhB gene plays an important role in conidiophore morphogenesis Taken together, these results suggest that the fkhA gene is necessary and sufficient for regulating sexual development and the fkhB gene is a transcription factor related in asexual developmental process in A. nidulans.

• Journal of Oral Medicine and Pain
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• v.48 no.2
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• pp.39-44
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• 2023

Primary Sjögren's syndrome (pSS) is an autoimmune progressive disease characterized by dysfunction and inflammation of the salivary glands. The underlying mechanisms of salivary gland involvement in pSS remain unclear, and researchers have primarily focused on immunological phenomena, making it difficult to distinguish between the cause and effect of the disease. Consequently, our research aims to directly investigate changes in homeostasis occurring in acinar cells, specifically in the context of muscarinic signaling, mucins, aquaporins, and forkhead box protein O1, to elucidate the initial step of pSS. We compare the disease-related phenomena observed in salivary gland acinar cells in pSS with the overall process of salivary secretion.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.4
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• pp.499-509
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• 2008

Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes preadipocyte differentiation of clonal cell lines from rodents. We isolated the full-length cDNA of porcine FoxO1 gene using RACE, confirmed by visual Northern blotting. The deduced amino acids indicated 94% and 90% identities with the corresponding human and mice aa. Analysis of the aa sequence, showed that it included a Forkhead domain (aa 167-247), a transmembrane structure domain (aa 90-113), a LXXLL motif (aa 469-473), and 51 Ser, 8 Thr, and 4 Tyr phosphorylation sites, indicating a potential important role for FoxO1 transcriptional activity in vivo. Using the IMpRH panel, we mapped FoxO1 gene to chromosome 11p13. Our data provide basic molecular information useful for the further investigation on the function of FoxO1 gene. Time-course analysis of FoxO1 expressions indicated that levels of mRNA and protein gradually increased from day 0 to 3, and it reached almost maximal level at day 3, then decreased from day 5 to 7 in porcine primary preadipocyte differentiation. After induction by IGF-1, GPDH activity and accumulation of lipid increased, however, expressions of FoxO1 mRNA and protein were inhibited in a dose dependent manner. These results suggest that FoxO1 takes part in porcine preadipocyte differentiation and expressions of FoxO1 were regulated by IGF-1.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10621-10625
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• 2015

Background: Increasing evidence has indicated that high Forkhead box protein C2 (FOXC2) level is closely associated with the development, progression, and poor prognosis of a variety of tumors. However, the relationship between FOXC2 and the progression of human gliomas remains to be clarified. The aim of present study was to assess FOXC2 expression and to explore its contribution in human gliomas. Materials and Methods: Realtime quantitative PCR was performed to examine FOXC2 expression in 85 pairs of fresh frozen glioma tissues and corresponding non-neoplastic brain tissues. Associations of FOXC2 expression with clinicopathological factors and prognosis of glioma patients were statistically analyzed. Results: The relative mRNA expression of FOXC2 was significantly higher in glioma tissues than the corresponding non-neoplastic brain tissues (p<0.001). In addition, high FOXC2 expression was significantly associated with advanced pathological grade (P=0.005) and the low Karnofsky performance score (KPS) (p=0.003), correlating with poor survival (p<0.001). Furthermore, multivariate Cox regression analysis showed that high FOXC2 expression was an independent predictor of overall survival (p=0.006). Conclusions: FOXC2 may act as an oncogenic gene and represent a potential regulator of aggressive development and a candidate prognostic marker in human gliomas.

• The Plant Pathology Journal
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• v.30 no.2
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• pp.136-150
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• 2014

Although multiple transcription factors (TFs) have been characterized via mutagenesis to understand their roles in controlling pathogenicity and infection-related development in Magnaporthe oryzae, the causal agent of rice blast, if and how forkhead-box (FOX) TFs contribute to these processes remain to be characterized. Four putative FOX TF genes were identified in the genome of M. oryzae, and phylogenetic analysis suggested that two of them (MoFKH1 and MoHCM1) correspond to Ascomycota-specific members of the FOX TF family while the others (MoFOX1 and MoFOX2) are Pezizomycotina-specific members. Deletion of MoFKH1 (${\Delta}Mofkh1$) resulted in reduced mycelial growth and conidial germination, abnormal septation and stress response, and reduced virulence. Similarly, ${\Delta}Mohcm1$ exhibited reduced mycelial growth and conidial germination. Conidia of ${\Delta}Mofkh1$ and ${\Delta}Mohcm1$ were more sensitive to one or both of the cell cycle inhibitors hydroxyurea and benomyl, suggesting their role in cell cycle control. On the other hand, loss of MoFOX1 (${\Delta}Mofox1$) did not show any noticeable changes in development, pathogenicity, and stress response. Deletion of MoFOX2 was not successful even after repeated attempts. Taken together, these results suggested that MoFKH1 and MoHCM1 are important in fungal development and that MoFKH1 is further implicated in pathogenicity and stress response in M. oryzae.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.167-176
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• 2023

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E₂ expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.

• Biomedical Science Letters
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• v.24 no.1
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• pp.15-22
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• 2018

Pristimerin is a triterpene compound isolated from plant extracts that reportedly possesses antitumor, antioxidant, and anti-inflammatory activities. The current study was designed to evaluate the antitumor effects of pristimerin on human colon cancer cells. Treatment of the human colon cancer cells, HCT116 and SW480, with pristimerin led to a dose-dependent decrease in cell proliferation. Flow cytometry experiments showed that pristimerin increased cell apoptotic rate and decreased the mitochondrial membrane potential in HCT116 and SW480 cells. Western blot assay showed that pristimerin induced increased cleavage of caspase-3, -7, -8, and poly ADP ribose polymerase. Treatment with pristimerin also caused a marked decrease in the expression of Bcl-2 and Bcl-xL. Additionally, the levels of phosphorylated AKT and forkhead box O3a (FOXO3a) were decreased in pristimerin-treated colon cancer cells. Taken together, our study illustrated that pristimerin promoted apoptosis via the AKT/FOXO3a signaling pathway in colon cancer cells, elucidating that it might be considered as a potential agent for colon cancer therapy.