• BMB Reports
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• 제47권7호
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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.

• BMB Reports
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• 제44권1호
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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.

• BMB Reports
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• 제43권3호
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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.

• Journal of Gastric Cancer
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• 제5권1호
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• pp.34-39
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• 2005

목적: KLF6는 모든 조직에서 발현되고 있는 zinc finger를 가진 종양억제유전자로 인체 여러 암에서 불활성화되어 있다. 연구자들은 KLF6 단백의 발현 변화가 위암의 발생에 관여하는 지를 알아보고자 하였다. 대상 및 방법: 85예의 파라핀 포매된 위암조직에서 암세포들으 각각 3군데에서 펀치하여 새로운 파라핀 블록으로 옮겨 위암의 tissue microarray를 제작하였다. Tissue microarray 절편에서 KLF6 단백에 대한 항체로 면역화학염색을 실시한 후 발현 양상을 병리 지표들인 조직학적 소견, 침습 정도, 림프절 전이 및 복막파종 등과의 연관성을 조사하였다. 결과: KLF6 단백은 위점막의 표면과 소와 상피세포에서 주로 발현되고 있었고 85예 중 28예($28.9\%$)에서 발현 소실이 관찰되었다. 흥미롭게도 KLF6 단백의 발현 소실은 림프절 전이와 통계적으로 연관성이 있었으나 조직학적 소견, 침습 정도와 복막파종과는 연관성이 없었다. 결론: 이러한 소견들은 KLF6 단백의 발현 소실이 위장관 상피세포의 비정상적인 성장과 분화를 유도하고 위암의 발생 및 진행에 관여한다는 것을 의미한다.

• BMB Reports
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• 제44권4호
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• pp.267-272
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• 2011

ZAS3 is a large zinc finger transcription repressor that binds the ${\kappa}B$-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed $NF{\kappa}B$-activated transcription by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of $NF{\kappa}B$. Here, we present evidence that upon $TNF{\alpha}$ stimulation, ZAS3 inhibits $NF{\kappa}B$-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on $NF{\kappa}B$ activity is mediated by neither direct association with $NF{\kappa}B$ nor disrupting nuclear localization of $NF{\kappa}B$. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of $NF{\kappa}B$, TRAF1 and TRAF2, thereby sensitizing cells to $TNF{\alpha}$-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.4137-4142
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• 2015

The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.

• Journal of Gastric Cancer
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• 제5권3호
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• pp.200-205
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• 2005

목적: Zinc finger를 가진 KLF4는 위장관 상피세포의 항상성 유지에 중요한 역할을 하는 종양억제유전자이다. 연구자들은 KLF4 단백의 발현 변화가 위암의 발생에 관여하는지를 파악하고 위암의 병리 지표들과 연관성이 있는지를 알아보고자 하였다. 대상 및 방법: 84예의 파라핀 포매된 위암조직에서 암세포들을 각각 3군데에서 펀치하여 새로운 파라핀 블록으로 옮겨 위암의 tissue microarray를 제작하였다. Tissue microarray 절편에서 KLF4 단백에 대한 항체로 면역화학염색을 실시한 후 발현 양상을 병리 지표들인 조직학적 소견, 침습 정도, 림프절 전이 및 복막파종 등과의 연관성을 조사하였다. 결과: KLF4 단백은 위점막의 표면과 소와 상피세포의 세포질과 핵에서 주로 발현되고 있었고 조사된 위암 84예 중 43예(51.2%)에서 발현이 현저히 저하되어 있거나 소실되어 있었다. 이러한 KLF4 단백의 발현 소실은 조직학적 소견, 침습 정도, 림프절 전이 및 복막파종과는 통계적으로 연관성이 없었다. 결론: 이러한 연구 결과는 KLF4 단백의 발현 소실이 위장관 상피세포의 비정상적인 성장과 분화를 유도하고 위암의 발생 초기에 관여한다는 것을 의미한다.

• Asian-Australasian Journal of Animal Sciences
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• 제19권9호
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• pp.1257-1261
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• 2006

Pleiomorphic adenoma gene-like1 (PLAGL1) encodes a zinc-finger (ZF) protein with seven ZFs of the C2H2-type which is a regulator of apoptosis and cell cycle arrest, and also regulates the secretion of insulin. In both human and mouse, PLAGL1 is a candidate gene for tumor suppressor and transient neonatal diabetes mellitus (TNDM). In this study, a 2,238 bp fragment covering the complete coding region was obtained and deposited to GenBank (accession number: DQ288899). The reverse transcriptase-polymerase chain reaction (RT-PCR) indicated that PLAGL1 was expressed almost equally in heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, fat, uterus and ovary. Comparing the sequences of Large White and Meishan pigs, a C-T transition in exon 6 was found. The polymorphism could be detected by TaqI and was genotyped in five purebreds (Large White, Landrace, Meishan, Tongcheng and Bamei). Association analysis was performed between the polymorphism and carcass traits in 276 pigs of a "Large White${\times}$Meishan" F2 resource population. As a consequence, significant associations of the genotypes with shoulder backfat thickness (SFT) and internal fat rate (IFR) were observed. Pigs with TT genotype had low SFT and high IFR compared with TC or CC genotypes.

• Molecules and Cells
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• 제26권5호
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• pp.443-453
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• 2008

The Bric-a-brac, Tramtrack, Broad-complex (BTB) domain is a protein-protein interaction domain that is found in many zinc finger transcription factors. BTB containing proteins play important roles in a variety of cellular functions including regulation of transcription, regulation of the cytoskeleton, protein ubiquitination, angiogenesis, and apoptosis. Here, we report the cloning and characterization of a novel human gene, KLHL31, from a human embryonic heart cDNA library. The cDNA of KLHL31 is 5743 bp long, encoding a protein product of 634 amino acids containing a BTB domain. The protein is highly conserved across different species. Western blot analysis indicates that the KLHL31 protein is abundantly expressed in both embryonic skeletal and heart tissue. In COS-7 cells, KLHL31 proteins are localized to both the nucleus and the cytoplasm. In primary cultures of nascent mouse cardiomyocytes, the majority of endogenous KLHL31 proteins are localized to the cytoplasm. KLHL31 acts as a transcription repressor when fused to GAL4 DNA-binding domain and deletion analysis indicates that the BTB domain is the main region responsible for this repression. Overexpression of KLHL31 in COS-7 cells inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). KLHL31 also significantly reduces JNK activation leading to decreased phosphorylation and protein levels of the JNK target c-Jun in both COS-7 and Hela cells. These results suggest that KLHL31 protein may act as a new transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions.

• Asian-Australasian Journal of Animal Sciences
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• 제32권4호
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• pp.494-500
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• 2019

Objective: Feed consumption contributes a large percentage for total production costs in the poultry industry. Detecting genes associated with feeding traits will be of benefit to improve our understanding of the molecular determinants for feed efficiency. The objective of this study was to identify candidate genes associated with feed conversion ratio (FCR) via genomewide association study (GWAS) using sequence data imputed from single nucleotide polymorphism (SNP) panel in a Chinese indigenous chicken population. Methods: A total of 435 Chinese indigenous chickens were phenotyped for FCR and were genotyped using a 600K SNP genotyping array. Twenty-four birds were selected for sequencing, and the 600K SNP panel data were imputed to whole sequence data with the 24 birds as the reference. The GWAS were performed with GEMMA software. Results: After quality control, 8,626,020 SNPs were used for sequence based GWAS, in which ten significant genomic regions were detected to be associated with FCR. Ten candidate genes, ubiquitin specific peptidase 44, leukotriene A4 hydrolase, ETS transcription factor, R-spondin 2, inhibitor of apoptosis protein 3, sosondowah ankyrin repeat domain family member D, calmodulin regulated spectrin associated protein family member 2, zinc finger and BTB domain containing 41, potassium sodium-activated channel subfamily T member 2, and member of RAS oncogene family were annotated. Several of them were within or near the reported FCR quantitative trait loci, and others were newly reported. Conclusion: Results from this study provide valuable prior information on chicken genomic breeding programs, and potentially improve our understanding of the molecular mechanism for feeding traits.