• Title/Summary/Keyword: Transcript factor

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Differential Expression of Cyclic AMP-Response Element Binding Protein Zhangfei (CREBZF) in the Mouse Testis during Postnatal Development

  • Jang, Hoon
    • Development and Reproduction
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    • v.22 no.1
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    • pp.65-72
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    • 2018
  • Cyclic AMP-response element binding protein zhangfei (CREBZF), a member of ATF/CREB (activating transcription factor/ cAMP response element binding protein) family, regulates numerous cellular functions and development of cells by interacting transcription factors. This study discovered the expression pattern of CREBZF in seminiferous tubule of testes during the postnatal development of mice. In testis, CREBZF mRNA expression was the highest among other organs. Immunofluorescence analyses showed that the CREBZF was specifically expressed on spermatocyte but not in spermatogonia and Sertoli cells in seminiferous epithelium of mouse testis. Semi-quantitative polymerase chain reaction (PCR) analysis showed that CREBZF transcript level was significantly elevated during postnatal development of mouse testis. Confocal imaging analysis indicated that the protein expression of CREBZF in seminiferous tubule remained low until postnatal day (PD) 14, and was dramatically increased in PD 21. Interestingly, only one type of the spermatocyte expressed CREBZF specifically among SCP3-positive spermatocytes. Taken together, these results suggest that CREBZF may be novel putative marker of the spermatocyte and regulate meiosis during postnatal development of mice.

Interleukin-32: Frenemy in cancer?

  • Han, Sora;Yang, Young
    • BMB Reports
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    • v.52 no.3
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    • pp.165-174
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    • 2019
  • Interleukin-32 (IL-32) was originally identified in natural killer (NK) cells activated by IL-2 in 1992. Thus, it was named NK cell transcript 4 (NK4) because of its unknown function at that time. The function of IL-32 has been elucidated over the last decade. IL-32 is primarily considered to be a booster of inflammatory reactions because it is induced by pro-inflammatory cytokines and stimulates the production of those cytokines and vice versa. Therefore, many studies have been devoted to studying the roles of IL-32 in inflammation-associated cancers, including gastric, colon cancer, and hepatocellular carcinoma. At the same time, roles of IL-32 have also been discovered in other cancers. Collectively, IL-32 fosters the tumor progression by nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$)-mediated cytokines and metalloproteinase production, as well as stimulation of differentiation into immunosuppressive cell types in some cancer types. However, it is also able to induce tumor cell apoptosis and enhance NK and cytotoxic T cell sensitivity in other cancer types. In this review, we will address the function of each IL-32 isoform in different cancer types studied to date, and suggest further strategies to comprehensively elucidate the roles of IL-32 in a context-dependent manner.

Identification and structure of AIMP2-DX2 for therapeutic perspectives

  • Hyeon Jin Kim;Mi Suk Jeong;Se Bok Jang
    • BMB Reports
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    • v.57 no.7
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    • pp.318-323
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    • 2024
  • Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-β and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-α. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers.

Isolation and Characterization of the gtfA Gene Encoding GAL4-Like Transcription Factor in Aspergillus nidulans (Aspergillus nidulans에서 GAL4 유사 전사인자를 암호화하는 gtfA 유전자의 분리 및 분석)

  • Park, Jae-Sin;Han, Dong-Min
    • Korean Journal of Microbiology
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    • v.49 no.1
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    • pp.8-16
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    • 2013
  • A GAL4 type transcription factor gene (formally annotated as AN3912) locating downstream of sndA (AN3911) was characterized. The putative transcription factor carries both Zn(II)2Cys6 binuclear cluster DNA-binding domain and transcription activator domain. The gene named gtfA (gal4 type transcription factor) had an open reading frame which consisted of 762 amino acids and was disrupted by three introns. The deletion mutant produced reduced amount of conidia but increased amount of fruiting bodies, suggesting that the GtfA make function in decision of asexual preferential to sexual development. The forced over expression of gtfA caused the retardation of fruiting body formation on high glucose concentration. The transcript level of gtfA was kept constant through the life cycle except late vegetative stage and early sexual development stage during which slight increase was found. The expression of gtfA was not significantly affected by sexual or asexual development regulators, such as VeA, NsdD or FluG, FadA, and SfaD. The GtfA repressed the nsdC transcription, which suggested that GftA control sexual development negatively via negative regulation of nsdC expression.

Insulin-like Growth Factor-I Induces Plectin and MACF1 Expression in C2C12 Myotubes (C2C12 myotube에서 insulin-like growth factor-I이 plectin과 MACF1 발현에 미치는 영향)

  • Kim, Hye Jin;Hwang, Ji Sun;Kwak, Yi-Sub;Lee, Won Jun
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1651-1657
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    • 2012
  • Plectin and microtubule actin cross-linking factor 1 (MACF1) are architectural proteins that contribute to the function of skeletal muscle as generators of mechanical force. However, the influence of insulin- like growth factor-I (IGF-I), a master regulator of skeletal muscle cells, on plectin and MACF1 in skeletal muscle cells has not been demonstrated. The effect of IGF-I on plectin and MACF1 gene expression was investigated by treating differentiated C2C12 murine skeletal muscle cells with 20 ng/ml of IGF-I at different time points. The IGF-I treatment increased plectin protein expression in a dose-dependent manner. The mRNA level of plectin was measured by real-time quantitative PCR to determine if plectin induction was regulated pretranslationally. IGF-I treatment resulted in a very rapid induction of plectin mRNA transcript in C2C12 myotubes. Plectin mRNA increased by 140 and 180% after 24 and 48 hours of IGF-I treatment, respectively, and returned to the control level after 72 hours of IGF-I treatment. MACF1 mRNA increased 86 and 90% after 24 and 48 hours of IGF-I treat-ment, respectively, and returned to the control level after 72 hours of IGF-I treatment. These results suggested that the plectin gene is regulated pretranslationally by IGF-I in skeletal muscle cells. In conclusion, IGF-I induces a rapid transcriptional modification of the plectin and MACF1 genes in C2C12 skeletal muscle cells and has modulating effects on a cytolinker protein as well as on contractile proteins.

H19 Gene Is Epigenetically Stable in Mouse Multipotent Germline Stem Cells

  • Oh, Shin Hye;Jung, Yoon Hee;Gupta, Mukesh Kumar;Uhm, Sang Jun;Lee, Hoon Taek
    • Molecules and Cells
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    • v.27 no.6
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    • pp.635-640
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    • 2009
  • Testis-derived germline stem (GS) cells can undergo reprogramming to acquire multipotency when cultured under appropriate culture conditions. These multipotent GS (mGS) cells have been known to differ from GS cells in their DNA methylation pattern. In this study, we examined the DNA methylation status of the H19 imprinting control region (ICR) in multipotent adult germline stem (maGS) cells to elucidate how epigenetic imprints are altered by culture conditions. DNA methylation was analyzed by bisulfite sequencing PCR of established maGS cells cultured in the presence of glial cell line-derived neurotrophic factor (GDNF) alone or both GDNF and leukemia inhibitory factor (LIF). The results showed that the H19 ICR in maGS cells of both groups was hypermethylated and had an androgenetic pattern similar to that of GS cells. In line with these data, the relative abundance of the Igf2 mRNA transcript was two-fold higher and that of H19 was three fold lower than in control embryonic stem cells. The androgenetic DNA methylation pattern of the H19 ICR was maintained even after 54 passages. Furthermore, differentiating maGS cells from retinoic acid-treated embryoid bodies maintained the androgenetic imprinting pattern of the H19 ICR. Taken together these data suggest that our maGS cells are epigenetically stable for the H19 gene during in vitro modifications. Further studies on the epigenetic regulation and chromatin structure of maGS cells are therefore necessary before their full potential can be utilized in regenerative medicine.

Fermented Unpolished Black Rice (Oryza sativa L.) Inhibits Melanogenesis via ERK, p38, and AKT Phosphorylation in B16F10 Melanoma Cells

  • Sangkaew, Orrarat;Yompakdee, Chulee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.8
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    • pp.1184-1194
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    • 2020
  • Melanin is a major factor that darkens skin color as one of the defense systems to prevent the harmful effects of UV light. However, darkened skin from the localized or systemic accumulation of melanin is viewed in many cultures as an esthetic problem. Consequentially, searching for anti-melanogenic agents from natural sources is very popular worldwide. Previous screening of fermented rice products, obtained from various rice cultivars fermented with different sources of loog-pang (Thai traditional fermentation starter), revealed that the highest ability to reduce the melanin content in B16F10 melanoma cells was from unpolished black rice fermented with a defined starter mixture of microbes isolated from loog-pang E11. The aim of this study was to investigate the mechanism of the fermented unpolished black rice (FUBR) on the inhibition of melanogenesis in B16F10 melanoma cells. The strongest reduction of cellular melanin content was found in the FUBR sap (FUBRS). The melanin reduction activity was consistent with the significant decrease in the intracellular tyrosinase activity. The FUBRS showed no cytotoxic effect to B16F10 melanoma or Hs68 human fibroblast cell lines. It also significantly reduced the transcript and protein expression levels of tyrosinase, tyrosinase-related protein 1 (TYRP-1), TYRP-2, and microphthalmia-associated transcription factor. Furthermore, it induced a significantly increased level of phosphorylated ERK, p38 and Akt signaling pathways, which likely contributed to the negative regulation of melanogenesis. From these results, a model for the mechanism of FUBRS on melanogenesis inhibition was proposed. Moreover, these results strongly suggested that FUBRS possesses anti-melanogenesis activity with high potential for cosmeceutical application as a skin depigmenting agent.

Effects of enamel matrix protein derivatives on the periodontal ligament like fibroblast and osteoblast like cells (법랑기질 단백질 유도체가 치주인대양세포 및 조골양세포에 미치는 영향)

  • Kim, Dong-Woon;Chung, Chin-Hyung;Lim, Sung-Bin;Ko, Seon-Yle
    • Journal of Periodontal and Implant Science
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    • v.33 no.2
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    • pp.225-246
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    • 2003
  • Recent study on the enamel matrix derivatives explained on the effects of new bone and new attachment formation in infrabony pocket of periodontal defects. The purpose of this study was to investigate on the biological effects of enamel matrix derivatives to attachment, proliferation and activation of periodontal ligament and osteoblast cells, After treatment of osteoblast and PDL cells with various Emdogain concentration level(0.03${\mu}g$/ml, 3${\mu}g$/ml, 300${\mu}g$/ml), activation of osteogenetic factor, calcified nodule formation and measuring alkaline phosphatase activity(ALP) were performed. 1. Both osteoblast and PDL cell showed increasing initial cell attachment with 300${\mu}g$/ml Emdogain concentration. 2. At the level of 300${\mu}g$/ml, accelerated proliferation of oseoblast and PDL cell was appeared. 3. As Emdogain's concentration increased, increased ALP activation of osteoblast was shown. In case of PDL cell, Emdogain increased ALP activation prominently at the level of 300${\mu}g$/ml. 4. No statistically significant activating change were founded at all of the concentrations of Emdogain on the activating of transcript factor Runx2 for differentiating osteoblast. 5. At the level of 300${\mu}g$/ml, calcified nodule formation was increased prominently to compare with other concentration. These results indicated that Emdogain should activate initial attachment, proliferation and activation, but not on Runx2 activation and can be used for useful tool of the treatment of periodontal tissue regeneration.

Analyses of Transcription Factor CP2 Expression during Development and Differentiation

  • Chae, Ji-Hyung;Oh, Eun-Jung;Kim, Chul-Geun
    • Animal cells and systems
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    • v.1 no.1
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    • pp.143-150
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    • 1997
  • Transcription factor CP2 was identified initially to bind the promoter region of the murine a-globin gene and its activity was shown to increase 2 to 3 fold during the induced differentiation of murine erythroleukemia (MEL) cells. To get further insight into the role of CP2 during development and differentiation, steady-state levels of CP2 message were monitored by using reverse transcriptase (RT)-PCR and in situ hybridization assays in the cultured MEL cells and differentiating embryonic stem (ES) cells in vitro, and in fetal and adult mouse tissues. The amount of CP2 messages increased 3 to 5 fold during induced differentiation of MEL cells, suggesting that the increment of CP2 activity during induced differentiation of MEL cells is originated from the increase of transcription initiation. On the other hand, CP2 expression is not restricted to the erythroid lineage cells; CP2 expressed ubiquitously from the undifferentiated ES cells to adult tissue cells. CP2 transcript was observed even in the undifferentiated ES cells and the level of expression increased from day 8 of the differentiating embryoid bodies. RT-PCR assay in the total RNAs prepared from several tissues of the adult mouse also showed ubiquitous expression profile, although the levels of expression were variable among tissues. When non-radioactive in situ hybridization assay was performed to the paraffin-sectioned whole body mouse embryos at days 11.5, 13.5, and 16.5 after fertilization, variable amounts of positive signals were also detected in different tissues.

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Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-κB-dependent pathway in the HEK293 cell line

  • Park, Yuk-Pheel;Choi, Seung-Chul;Kim, Bo-Yeon;Kim, Jong-Tae;Song, Eun-Young;Kang, Seong-Ho;Yoon, Do-Young;Paik, Sang-Gi;Kim, Kwang-Dong;Kim, Jong-Wan;Lee, Hee-Gu
    • BMB Reports
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    • v.41 no.11
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    • pp.784-789
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    • 2008
  • Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immuno-fluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-${\kappa}B$ binding. p65 and p50-NF-${\kappa}B$ are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-${\kappa}B$ pathway.