• Title/Summary/Keyword: zinc-finger

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Zinc finger and BTB domain-containing protein 3 is essential for the growth of cancer cells

  • Lim, Ji-Hong
    • BMB Reports
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    • v.47 no.7
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    • pp.405-410
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    • 2014
  • ZBTB3 belongs to the Zinc finger and BTB/POZ domain containing transcription factor family; however, its biological role has rarely been studied. We demonstrate for the first time, to our knowledge, that ZBTB3 is an essential factor for cancer cell growth via the regulation of the ROS detoxification pathway. Suppression of ZBTB3 using two different short hairpin RNAs in human melanoma, lung carcinoma, and breast carcinoma results in diminished cell growth. In addition, we found that suppression of ZBTB3 activates a caspase cascade, including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from failed ROS detoxification. We identified that ZBTB3 plays an important role in the gene expression of ROS detoxification enzymes. Our results reveal that ZBTB3 may play a critical role in cancer cell growth via the ROS detoxification system. Therefore, therapeutic strategies that target ZBTB3 could be used in selective cancer treatments.

Development of Anti-Fingers Printed EGI Steel Sheet With High Corrosion Resistance (고내식성 내지문 EGI 강판 개발)

  • 김형준
    • Journal of the Korean institute of surface engineering
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    • v.26 no.6
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    • pp.307-315
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    • 1993
  • A study on a new anti-finger printed EGI steel sheet with high corrosion resistance has been carried out to meet the recent requirement of high quality and performance of the pure zinc electrogalvanized steel sheet. The substrate was the pure zinc electrogalvanized sheet with the metallic coating of 20g/$\m^2$. The two differ-ent processes for inorganic(chromating) and organic(resin) coating were applied. One was a two coat/two bake type to separately treat chromating and resin coating which is now widely used. The other was a one coat/one bake type to simultaneously treat them which is newly developed in this study. The solution for the one coat/one bake type was an aqua-base coating agents which was composed of inorganic and organic components. The new anti-finger printed EGI steel sheet with the Cr and resin coating weight of 13mg/$\m^2$ and 800mg/$\m^2$, respectively shows the superior corrosion resistance besides the good paintability, formability fingerprint resistance and earth characteristics properties.

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Production of Mutated Porcine Embryos Using Zinc Finger Nucleases and a Reporter-based Cell Enrichment System

  • Koo, Ok Jae;Park, Sol Ji;Lee, Choongil;Kang, Jung Taek;Kim, Sujin;Moon, Joon Ho;Choi, Ji Yei;Kim, Hyojin;Jang, Goo;Kim, Jin-Soo;Kim, Seokjoong;Lee, Byeong-Chun
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.3
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    • pp.324-329
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    • 2014
  • To facilitate the construction of genetically-modified pigs, we produced cloned embryos derived from porcine fibroblasts transfected with a pair of engineered zinc finger nuclease (ZFN) plasmids to create targeted mutations and enriched using a reporter plasmid system. The reporter expresses RFP and eGFP simultaneously when ZFN-mediated site-specific mutations occur. Thus, double positive cells ($RFP^+/eGFP^+$) were selected and used for somatic cell nuclear transfer. Two types of reporter based enrichment systems were used in this study; the cloned embryos derived from cells enriched using a magnetic sorting-based system showed better developmental competence than did those derived from cells enriched by flow cytometry. Mutated sequences, such as insertions, deletions, or substitutions, together with the wild-type sequence, were found in the cloned porcine blastocysts. Therefore, genetic mutations can be achieved in cloned porcine embryos reconstructed with ZFN-treated cells that were enriched by a reporter-based system.

Ecophysiological Changes in a Cold Tolerant Transgenic Tobacco Plant Containing a Zinc Finger Protein (PIF1) Gene

  • Yun, Sung-Chul;Kwon, Hawk-Bin
    • Korean Journal of Environmental Agriculture
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    • v.27 no.4
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    • pp.389-394
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    • 2008
  • The ecophysiological changes occurring upon cold stress were studied using cold tolerant transgenic and wild-type tobacco plants. In a previous study, cold tolerance in tobacco was induced by the introduction of a gene encoding the zinc finger transcription factor, PIF1. Gas-exchange measurements including net photosynthesis and stomatal conductance were performed prior to, in the middle of, and after a cold-stress treatment of $1{\pm}2^{\circ}C$ for 96 h in each of the four seasons. In both transgenic and wild-type plants, gas-exchange parameters were severely decreased in the middle of the cold treatment, but had recovered after 2-3 h of adaptation in a greenhouse. Most t-test comparisons on gas-exchange measurements between the two plant types did not show statistical significance. Wild-type plants had slightly more water-soaked damage on the leaves than the transgenic plants. A light-response curve did not show any differences between the two plant types. However, the curve for assimilation-internal $CO_2$ in wild-type plants showed a much higher slope than that of the PIF1 transgenic plants. This means that the wild-type plant is more capable of regenerating Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and has greater electron transport capacity. In conclusion, cold-resistant transgenic tobacco plants demonstrated a better recovery of net photosynthesis and stomatal conductance after cold-stress treatment compared to wild-type plants, but the ecophysiological recoveries of the transgenic plants were not statistically significant.

A novel human KRAB-related zinc finger gene ZNF425 inhibits mitogen-activated protein kinase signaling pathway

  • Wang, Yuequn;Ye, Xiangli;Zhou, Junmei;Wan, Yongqi;Xie, Huaping;Deng, Yun;Yan, Yan;Li, Yongqing;Fan, Xiongwei;Yuan, Wuzhou;Mo, Xiaoyang;Wu, Xiushan
    • BMB Reports
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    • v.44 no.1
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    • pp.58-63
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    • 2011
  • Zinc finger (ZNF) proteins play a critical role in cell growth, proliferation, apoptosis, and intracellular signal transduction. In this paper, we cloned and characterized a novel human KRAB-related zinc finger gene, ZNF425, which encodes a protein of 752 amino acids. ZNF425 is strongly expressed in the three month old human embryos and then is almost undetectable in six month old embryos and in adult tissues. An EGFP-ZNF425 fusion protein can be found in both the nucleus and the cytoplasm. ZNF425 appears to act as a transcription repressor. Over-expression of ZNF425 inhibits the transcriptional activities of SRE, AP-1, and SRF. Deletion analysis indicates that the C2H2 domain is the main region responsible for the repression. Our results suggest that the ZNF425 gene is a new transcriptional inhibitor that functions in the MAPK signaling pathway.

ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway

  • Wang, Yuequn;Zhou, Junnei;Ye, Xiangli;Wan, Yongqi;Li, Youngqing;Mo, Xiaoyan;Yuan, Wuzhou;Yan, Yan;Luo, Na;Wang, Zequn;Fan, Xiongwei;Deng, Yun;Wu, Xiushan
    • BMB Reports
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    • v.43 no.3
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    • pp.212-218
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    • 2010
  • Zinc finger-containing transcription factors are the largest single family of transcriptional regulators in mammals, which play an essential role in cell differentiation, cell proliferation, apoptosis, and neoplastic transformation. Here we have cloned a novel KRAB-related zinc finger gene, ZNF424, encoding a protein of 555aa. ZNF424 gene consisted of 4 exons and 3 introns, and mapped to chromosome 19p13.3. ZNF424 gene was ubiquitously expressed in human embryo tissues by Northern blot analysis. ZNF424 is conserved across species in evolution. Using a GFP-labeled ZNF424 protein, we demonstrate that ZNF424 localizes mostly in the nucleus. Transcriptional activity assays shows ZNF424 suppresses transcriptional activity of L8G5-luciferase. Overexpression of ZNF424 in HEK-293 cells inhibited the transcriptional activity of NFAT and p21, which may be silenced by siRNA. The results suggest that ZNF424 protein may act as a transcriptional repressor that suppresses NFAT and p21 pathway to mediate cellular functions.

Expression Pattern of KLF6 in Korean Gastric Cancers (한국인 위암에서 KLF6 단백 발현 양상)

  • Cho Young Gu;Kim Chang Jae;Park Cho Hyun;Kim Su Young;Nam Suk Woo;Lee Sug Hyung;Yoo Nam Jin;Lee Jung Young;Park Won Sang
    • Journal of Gastric Cancer
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    • v.5 no.1
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    • pp.34-39
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    • 2005
  • Purpose: KLF6, a member of the KLF family, is a ubiquitous zinc finger tumor suppressor protein that is mutated in several human cancers. Our aim was to determine whether the expression pattern of KLF6 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 85 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF6 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF6 protein was expressed on superficial and foveolar epithelial cells in the gastric mucosa. We found loss of KLF6 expression in 28 ($32.9\%$) of the 85 gastric cancer tissues. There was a significant correlation between loss of KLF6 expression and lymph-node metastasis. However, other pathologic parameters, such as histologic type, depth of invasion, and peritoneal dissemination, were not statistically associated with loss of KLF6 expression. Conclusion: Our findings suggest that loss of KLF6 expression may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development and/or progression of Korean gastric cancer.

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A Splice Variant of the C2H2-Type Zinc Finger Protein, ZNF268s, Regulates NF-κB Activation by TNF-α

  • Chun, Jung Nyeo;Song, In Sung;Kang, Dong-Hoon;Song, Hye Jin;Kim, Hye In;Suh, Ja Won;Lee, Kong Ju;Kim, Jaesang;Won, Sang
    • Molecules and Cells
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    • v.26 no.2
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    • pp.175-180
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    • 2008
  • $I{\kappa}B$ kinase (IKK), the pivotal kinase in signal-dependent activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), is composed of multiple protein components, including IKK ${\alpha}/{\beta}/{\gamma}$ core subunits. To investigate the regulation of the IKK complex, we immunoaffinity purified the IKK complex, and by MALDI-TOF mass spectrometry identified a splice variant of zinc finger protein 268 (ZNF268) as a novel IKKinteracting protein. Both the full-length and the spliced form of the ZNF268 protein were detected in a variety of mammalian tissues and cell lines. The genes were cloned and expressed by in vitro transcription/translation. Several deletion derivatives, such as KRAB domain (KRAB) on its own, the KRAB/spacer/4-zinc fingers (zF4), and the spacer/4-zinc fingers (zS4), were ectopically expressed in mammalian cells and exhibited had different subcellular locations. The KRAB-containing mutants were restricted to the nucleus, while zS4 was localized in the cytosol. TNF-${\alpha}$-induced NF-${\kappa}B$ activation was examined using these mutants and only zS4 was found to stimulate activation. Collectively, the results indicate that a spliced form of ZNF268 lacking the KRAB domain is located in the cytosol, where it seems to play a role in TNF-${\alpha}$-induced NF-${\kappa}B$ activation by interacting with the IKK complex.

Zinc modulation of osterix in MC3T3-E1 cells

  • Seo, Hyun-Ju;Jeong, Jin Boo;Cho, Young-Eun;Kwun, In-Sook
    • Journal of Nutrition and Health
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    • v.53 no.4
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    • pp.347-355
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    • 2020
  • Purpose: Zinc is known to be associated with osteoblast proliferation and differentiation. Osterix as zinc-finger transcription factor is also related to osteoblast differentiation and bone formation. In the present study, we aimed to investigate whether zinc modulates osterix gene and protein expression in osteoblastic MC3T3-E1 cells. Methods: MC3T3-E1 cells were cultured in zinc-dependent concentrations (0, 0.5, 1, 5, or 15 µM Zn), along with osteogenic control (normal osteogenic medium) for 1 and 3 days. The gene and protein expression levels of osterix were analyzed by real-time reverse transcription polymerase chain reaction and Western blotting, respectively. Results: Zinc increased osteoblast proliferation in a concentration-dependent manner at day 1 and 3. Similarly, zinc increased the activity of osteoblast marker enzyme alkaline phosphatase in cells and media in a zinc concentration-dependent manner. Moreover, our results showed that the pattern of osterix gene expression by zinc was down-regulated within the low levels of zinc treatments (0.5-1 µM) at day 1, but it was up-regulated after extended culture period at day 3. Osterix protein expression by zinc showed the similar pattern of gene expression, which down-regulated by low zinc levels at day 1 and up-regulated back at day 3 as the early stage of osteoblast differentiation. Conclusion: Our results suggest that zinc modulates osterix gene and protein expression in osteoblasts, particularly in low level of zinc at early stage of osteoblast differentiation period.