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Xiaoying Zhan,
Wenting Wu,
Baohui Han,
Ge Gao,
Rong Qiao,
Juan Lv,
Shuyu Zhang,
Wei Zhang,
Weiwei Fan,
Hongyan Chen,
Tianbao Zhang,
Aiqin Gu,
Jie Shen, Qihan Wu,
Daru Lu
[show abstract]
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ABSTRACT: Rs11614913 is a polymorphism in hsa-miR-196a2 reported to alter mature microRNA expression and function. This single-nucleotide polymorphism (SNP) was reported to be associated with susceptibility and prognosis of lung cancer.
In this article, association study was performed to reveal the relation between SNP and response rate or severe toxicity after platinum-based regimen in advanced nonsmall cell lung cancer patients.
By screening this polymorphism in 442 Chinese patients with MALDI-TOF Mass Spectrometer, significantly higher occurrence of grade 3 or 4 overall toxicity (P = 0.02) in response to treatment was found in patients with homozygous CC. After stratified analyses, association between rs11614912 and overall toxicity existed, especially in individuals treated with gemcitabine (P = 0.006) or cisplatin (P = 0.008), and in male patients (P = 0.02) or younger patients (P = 0.01).
Our study confirmed that rs11614913 in hsa-miR-196a2 was associated with severe toxicity in lung cancer patients, and might help to improve individualized therapy in the future.
Journal of Clinical Laboratory Analysis 11/2012; 26(6):441-6. · 1.38 Impact Factor
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Ji Qian,
Hui-Qi Qu,
Lixin Yang,
Ming Yin,
Qiming Wang,
Shaohua Gu, Qihan Wu,
Xueying Zhao,
Wenting Wu,
Junjie Wu,
Xiaoming Tan,
Wenqing Chen,
Haijian Wang,
Jiucun Wang,
Weiwei Fan,
Hongyan Chen,
Baohui Han,
Daru Lu,
Qingyi Wei,
Li Jin
[show abstract]
[hide abstract]
ABSTRACT: Caspase-8 and caspase-10 play crucial roles in both cancer development and chemotherapy efficacy. In this study, we aimed to comprehensively assess single nucleotide polymorphisms (SNPs) of the caspase-8 (CASP8) and caspase-10 (CASP10) genes in relation to toxicity outcomes with first-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 13 tag SNPs of CASP8 and CASP10 in 663 patients with advanced NSCLC treated with platinum-based chemotherapy regimens. Associations between SNPs and chemotherapy toxicity outcomes were identified in a discovery set of 279 patients and then validated in an independent set of 384 patients. In both the discovery and validation sets, variant homozygotes of CASP8 rs12990906 and heterozygotes of CASP8 rs3769827 and CASP10 rs11674246 and rs3731714 had a significantly lower risk for severe toxicity overall. However, only the association with the rs12990906 variant was replicated in the validation set for hematological toxicity risk. In a stratified analysis, we found that some other SNPs, including rs3769821, rs3769825, rs7608692, and rs12613347, were significantly associated with severe toxicity risk in some subgroups, such as in nonsmoking patients, patients with adenocarcinoma, and patients treated with cisplatin combinations. Consistent results were also found in haplotype analyses. Our results provide novel evidence that polymorphisms in CASP8 and CASP10 may modulate toxicity outcomes in patients with advanced NSCLC treated with platinum-based chemotherapy. If validated, the findings will facilitate the genotype-based selection of platinum-based chemotherapy regimens.
The Oncologist 07/2012; · 3.91 Impact Factor
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Shaohua Gu, Qihan Wu,
Xueying Zhao,
Wenting Wu,
Zhiqiang Gao,
Xiaoming Tan,
Ji Qian,
Hongyan Chen,
Yi Xie,
Li Jin,
Baohui Han,
Daru Lu
[show abstract]
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ABSTRACT: Apoptosis is a distinct mode of cell death that is responsible for the deletion of cells in tumors and in normal tissues. We pursued a pathway-based approach to investigate the association of potentially functional genetic polymorphisms of the corresponding genes with the outcomes of platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). A MALDI-TOF mass spectrometer was used for genotyping 10 polymorphisms of eight apoptosis-related genes, including BCL2 rs1801018, rs1564483, rs2279115, BAX rs4645878, caspase (CASP3) rs6948, CASP8 rs3834129, CASP10 rs13006529, rs3900115, tumor necrosis factor α (TNFα) rs1800629, and macrophage migration inhibitory factor (MIF) rs755622. The associations between these single nucleotide polymorphisms and the outcomes of 445 advanced NSCLC patients treated with platinum-based chemotherapy were evaluated. The CASP3 rs6948 polymorphism was most significantly associated with hematologic toxicity in a dose-dependent manner. The incidence of severe hematologic toxicity was significantly lower in C allele carriers (P = 0.005; odds ratio = 0.524; 95% confidence interval = 0.333-0.824) and still significant after a Bonferroni correction. The function of this single nucleotide polymorphism in gene expression was also investigated. Quantitative PCR showed that individuals with the C allele had lower levels of CASP3 transcripts in peripheral blood lymphocytes. Luciferase reporter assays showed that the minor C allele significantly decreased the reporter gene expression level. In addition, the TNFα rs1800629 mutant allele significantly elevated gastrointestinal toxicity (P = 0.020; odds ratio = 3.020; 95% confidence interval = 1.188-7.676), when compared to the wild-type homozygote. No other association was found. In conclusion, for the first time, our study suggests that CASP3 rs6948 might influence CASP3 expression and be associated with severe hematologic toxicity risk.
Cancer Science 05/2012; 103(8):1451-9. · 3.33 Impact Factor
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Ji Qian,
Shaohua Gu, Qihan Wu,
Xueying Zhao,
Wenting Wu,
Zhiqiang Gao,
Wei Zhang,
Xiaoming Tan,
Haijian Wang,
Jiucun Wang,
Weiwei Fan,
Hongyan Chen,
Baohui Han,
Daru Lu,
Qingyi Wei,
Li Jin
[show abstract]
[hide abstract]
ABSTRACT: Abstract BACKGROUND:CASP7 plays a crucial role in cancer development and chemotherapy efficacy. We therefore explored whether single nucleotide polymorphisms (SNPs) of the CASP7 gene can modulate outcomes of advanced non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy. METHODS:We systematically genotyped 17 SNPs of CASP7 first in a discovery set of 279 patients with advanced NSCLC treated with platinum-based chemotherapy and then replicated the results in an independent set of 384 patients, in which we evaluated their associations with overall survival (OS) and progress free survival (PFS) by Kaplain-Meier analysis and Cox-hazards regression analysis. RESULTS:In both discovery and validation sets as well as in the pooled analysis, heterozygotes of CASP7 rs2227310 and rs4353229 as well as rs12415607 variant allele were strongly associated with a better OS of NSCLC (in the pooled sample: adjusted HR: 0.73, 95% CI = 0.59-0.90, P = 0.003; HR: 0.72, 95% CI =0.59-0.89, P = 0.002; and HR: 0.76, 95% CI = 0.62-0.94, P = 0.009, respectively). In stratified analyses of the pooled dataset, treated with paclitaxel, individuals carrying variant allele of rs2227310, rs4353229 and rs12415607 had significantly improved OS (HR: 0.60, 95% CI = 0.41-0.87, P = 0.008; HR: 0.58, 95% CI = 0.39-0.84, P = 0.004; and HR: 0.61, 95% CI = 0.42-0.89, P = 0.010; respectively). CONCLUSIONS:This study provides evidence that genetic variations of CASP7 may modulate OS and PFS of patients with advanced NSCLC treated with platinum-based chemotherapy.
Chest 03/2012; · 5.25 Impact Factor
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Zhenchao Ruan,
Yao Zhao,
Lili Yan,
Hongyan Chen,
Weiwei Fan,
Juxiang Chen, Qihan Wu,
Ji Qian,
Tianbao Zhang,
KeKe Zhou,
Yin Mao,
Liangfu Zhou,
Yan Huang,
Daru Lu
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ABSTRACT: Gliomas are aggressive brain tumor. Association studies were consistent for an inverse association between asthma and allergic conditions (IgE levels) and risk of glioma. Studies reported that the IL-4Ra, IL-13 and STAT6 genes played a relatively strong role in IgE production or allergy. This population-based case-control study aimed to find potential association between single nucleotide polymorphisms IL-13rs20541, IL-4Rars1801275 and glioma susceptibility in population, as well as STAT6 rs1059513 and STAT6 rs324015. Among non-smokers, homozygote GG of STAT6 4610A/G showed an increased association with risk of glioma compared with AA (adjusted OR=1.691, 95%CI=1.152-2.481, p=0.007, corrected p=0.028), and the haplotype with A allele at rs1059513 and G allele at rs324015 was revealed to increase glioma risk significantly (OR=1.321,95%CI= 1.081-1.614, p=0.007,corrected p=0.028). GG genotype of STAT6 4610A/G was a significant risk factor compared with AA in glioblastoma (adjusted OR=1.856, 95%CI=1.153-2.987, p=0.011, corrected p=0.044). GG of STAT6 4610A/G was significantly related to increased WHO IV risk compared with AA (adjusted OR=1.591,95%CI=1.030-2.459, p=0.036, corrected p=0.144). Interaction between IL-13 Arg130Gln and IL-4Ra Gln576Arg was observed in decreasing glioma risk (p=0.045).
Frontiers in bioscience (Elite edition) 01/2011; 3:33-45.
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Qihan Wu,
Xiaoying Zhan,
Tonghai Dou,
Hongyan Chen,
Weiwei Fan,
Keke Zhou,
Haishi Zhang,
Hongxia Zheng,
Yanyan Cai,
Yao Zhao,
Fengping Huang,
Liangfu Zhou,
Ying Mao,
Daru Lu
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ABSTRACT: Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) A49G is a polymorphism that is extensively studied in various cancers. To investigate whether it is associated with the occurrence of glioma in Chinese patients, we performed a case-control research study with 670 patients and 680 controls. In this group, we found that the genotype at this locus is significantly associated with glioma risk (GG vs. AA: P = 0.045; GG + AG vs. AA: P = 0.013). In some subgroups, G allele carriers are significantly less represented. We also observed significant correlations between the polymorphism genotype and glioma risk in patients with WHO histologic stages. We conclude that CTLA4 A49G might be a potential clinical biomarker for distinguishing persons with a high risk for developing gliomas.
Biochemical Genetics 12/2010; 49(3-4):190-201. · 0.86 Impact Factor
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Juxiang Chen, Qihan Wu,
Yicheng Lu,
Tao Xu,
Yan Huang,
Judit Ribas,
Xiaohua Ni,
Guohan Hu,
Fengping Huang,
Liangfu Zhou,
Daru Lu
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ABSTRACT: SPP1 was found to be significantly upregulated in many kinds of malignant tumors, including gliomas. Considering that gene polymorphisms have been implicated in the development of gliomas, we performed an association study between SPP1 functional promoter region polymorphisms and glioma risk in a Chinese population. We found significant evidence of an association between SPP1 promoter polymorphisms and glioma risk. For the -155_156insG variant, the -155_156GG allele was found to be significantly associated with an increased risk of glioma (P=0.020, odds ratio (OR)=1.202, 95% confidence interval (CI): 1.028-1.408). Individuals with the genotype containing the GG allele had a 1.372-fold increased risk (P=0.006, OR=1.372, 95% CI: 1.095-1.719). Further stratified analyses suggested that a significant association existed in adult glioma patients, male subjects and in cases without a family history of cancer. Alternatively, the study of single-nucleotide polymorphism -443C/T in a recessive model revealed that the genotype CC+CT significantly decreased the risk of glioma when compared with TT (P=0.023, OR=0.774, 95% CI: 0.621-0.966). After the analysis of haplotypes, the haplotype -155_156GG/-443T was represented at a significantly higher frequency in cases (P=0.029, OR=1.192, 95% CI: 1.018-1.395). Cellular assay indicated that the transcriptional activity of the SPP1 promoter containing the -155_156GG allele significantly increased in glioma cells. Thus, variants of the SPP1 promoter might influence the risk of glioma by regulating promoter activity. Further analyses are necessary to validate our observation in larger samples or in other ethnic groups.
Journal of Human Genetics 07/2010; 55(7):456-61. · 2.57 Impact Factor
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Shuyu Zhang,
Juan Lu,
Xueying Zhao,
Wenting Wu,
Huibo Wang,
Jun Lu, Qihan Wu,
Xin Chen,
Weiwei Fan,
Hongyan Chen,
Feng Wang,
Zhibin Hu,
Li Jin,
Qingyi Wei,
Hongbing Shen,
Wei Huang,
Daru Lu
[show abstract]
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ABSTRACT: Checkpoint kinase (CHEK) 2, a tumor suppressor gene, plays an essential role in the DNA damage checkpoint response cascade. We first investigated two polymorphisms in the proximal promoter of the CHEK2 gene and evaluated their associations with the risk of lung cancer in a case-control study using 500 incident lung cancer cases and 517 cancer-free controls. We found that CHEK2 rs2236141 -48 G > A was significantly associated with lung cancer risk (P = 0.0018). Similar results were obtained in a follow-up replication study in 575 lung cancer patients and 589 controls (P = 0.042). Quantitative polymerase chain reaction showed that individuals with the G allele had lower levels of CHEK2 transcripts in peripheral blood mononuclear cells and normal lung tissues. The -48 G-->A variant eliminated a methylation site and thereby relieve the transcriptional repression of CHEK2. Therefore, this polymorphism affected downstream transcription through genetic and epigenetic modifications. Luciferase reporter assays demonstrated that the major G allele significantly attenuated reporter gene expression when methylated. Electrophoretic Mobility shift assays and surface plasmon resonance revealed that the methylated G allele increased transcription factor accessibility. We used in vivo chromatin immunoprecipitation to confirm that the relevant transcription factor was Sp1. Using lung tissue heterozygous for the G/A single-nucleotide polymorphism, we found that Sp1 acted as a repressor and had a stronger binding affinity for the G allele. These results support our hypothesis that the CHEK2 rs2236141 variant modifies lung cancer susceptibility in the Chinese population by affecting CHEK2 expression.
Carcinogenesis 05/2010; 31(7):1251-8. · 5.70 Impact Factor
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ABSTRACT: G protein-coupled receptors (GPCRs) are critical factors in regulating morphogenesis, mating, infection and virulence in fungi. In this study, various computational strategies were applied to identify GPCR-like proteins from the genomes of both Verticillium dahliae and Verticillium albo-atrum. The putative GPCRs were distributed over 13 classes, and significantly, three of those represented novel classes of GPCR-like proteins in fungi. The three novel GPCRs had high levels of identity to their counterparts in higher eukaryotes, including Homo sapiens. The numbers of GPCR-like proteins in the two Verticillium spp. were similar to those seen in other filamentous fungi, such as Magnaporthe grisea, Neurospora crassa and Fusarium graminearum. Additionally, the carbon/amino acid receptors were divided into three different subclasses, indicating that differences among the GPCRs existed not only among different classes but also within classes. In conclusion, the identification and classification of GPCRs and their homology to some well-studied fungi will be an important starting point for future research in Verticillium spp.
Fungal Biology 04/2010; 114(4):359-68. · 1.43 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in regulation of eukaryotic gene expression. Aberrant expression and structural alternation of miRNAs are considered to participate in tumorigenesis and cancer development. Recently, different genotypes of miR-196a polymorphisms (SNP, rs11614913) were found to be associated with the survival of patients with lung cancer and increased risk of breast cancer. To further investigate whether this polymorphism may influence glioma risk or not, we examined the SNP allele frequency in Chinese population. Our data shows the genotype CC of miR-196a (rs11614913) polymorphism is associated with decreased risk of glioma in the Chinese population (OR = 0.74, 95% CI:0.56-0.98). Furthermore, a significant association was observed between this genotype and glioma risk in the subgroups of adult glioma (OR = 0.73, 95% CI:0.55-0.98), male glioma (OR = 0.69, 95% CI:0.48-0.99) and patients with glioblastoma (OR = 0.58, 95% CI:0.37-0.91). This was the first study investigating the association between the miR-196a rs11614913 and glioma risk. Compared with the results from previous studies in lung cancer and breast cancer, our data suggest a different genotype association in glioma. This may be related to the diversity on the tissue origin, tumor type, tumorigenesis, and developing process.
Journal of Cancer Research and Clinical Oncology 03/2010; 136(12):1853-9. · 2.56 Impact Factor
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Shujie Wang,
Yao Zhao,
Zhenchao Ruan,
Hongyan Chen,
Weiwei Fan,
Juxiang Chen, Qihan Wu,
Ji Qian,
Tianbao Zhang,
Yan Huang,
Daru Lu
[show abstract]
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ABSTRACT: Epidermal growth factor (EGF) is critical in cancer process. EGF and EGF receptor (EGFR) interaction plays a pivotal role in cell proliferation, differentiation, and tumorigenesis of epithelial tissues. Variations of the EGF +61G/A (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to brain glioma. The purpose of this study was to investigate the potential association between EGF +61G/A and brain glioma in a Chinese population.
In this study, we analyzed single nucleotide polymorphism of EGF +61G/A in 677 patients with glioma and 698 gender- and age-matched controls. Genotyping was performed by polymerase chain reaction-ligation detection reaction (PCR-LDR) method.
The A allele (minor Allele) was 33.0% in cases and 27.3% in controls. The additive model was more powerful to reveal the association in our study than that of recessive and dominant model. Our data showed the genotype G/A and A/A was associated with increased risk for glioma (adjusted OR = 1.48, 95%CI: 1.17-1.87, p = 0.001 for G/A, adjusted OR = 1.81, 95%CI: 1.20-2.72, p = 0.005 for A/A, respectively), and for glioblastoma (adjusted OR = 1.51, 95%CI: 1.06-2.17, p = 0.024 and adjusted OR = 2.35, 95%CI: 1.34-4.15, p = 0.003, respectively). The A allele significantly increased glioma risk (OR = 1.31, 95%CI: 1.11-1.55, p = 0.001). The additive model (G/G vs G/A vs A/A) showed that both G/A and A/A genotype increased glioma risk (adjusted OR = 1.40, 95% CI: 1.17-1.66, p = 0.0002).G/A and A/A genotypes or EGF +61 A allele increased risk in both low and high WHO grade glioma. Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers.
Our study indicated that G/A and A/A genotypes or EGF +61 A allele were associated with higher glioma risk in Chinese. This is in contrast with previous studies which reported G allele as a risk factor of glioma in Caucasian. The role of EGF +61 A/G polymorphism in glioma susceptibility needs further investigation.
BMC Cancer 01/2010; 10:221. · 3.01 Impact Factor
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ABSTRACT: Insulin-like growth factor-I modulates cell growth and survival, and is thought to be important in tumor development. A (CA)19 repeat polymorphism in the promoter region of IGF-I gene that may affect transcription activity has been implicated as a risk factor for cancer, but individual studies have been inconclusive or controversial. Therefore, we performed a meta-analysis of 17 studies with IGF-I (CA)19 repeat genotyping on 8,799 patients and 13,901 controls. There were seven studies with prostate cancer (2,307 cases; 2,622 controls), seven studies with breast cancer (3,533 cases; 7,771 controls), and three studies with colorectal cancer (2,959 cases; 3,508 controls). Overall, the random effects odds ratio (OR) for the (CA)19 versus non-(CA)19 allele was 1.03 [95% confidence interval (CI), 0.95-1.11], with some between-study heterogeneity (P < 0.0001). There was no suggestion of an overall effect either in recessive or dominant modeling of (CA)19 allele effects, and the comparison of (CA)19 homozygosity versus non-(CA)19 homozygosity also showed no differential susceptibility to cancer (OR, 0.99; 95% CI, 0.84-1.16). No effect of (CA)19 was seen in subjects of breast cancer (seven comparisons, OR = 1.03; 95% CI, 0.90-1.17, P = 0.005 for heterogeneity), prostate cancer (seven comparisons, OR = 1.08; 95% CI, 0.88-1.27; P = 0.0002 for heterogeneity) and colorectal cancer (three comparisons, OR = 0.96; 95% CI, 0.89-1.03, P = 0.36, no significant between-study heterogeneity). There was also no evidence that the (CA)19 allele associated with the risk of cancer in Caucasians and Asians. The meta-analysis shows that this (CA)19 repeat polymorphism is unlikely to be a major determinant of susceptibility to cancer on a wide population basis. However, a larger single study is required to further evaluate the association IGF-I (CA)19 polymorphisms and the cancer risk in a specific population.
Journal of Human Genetics 01/2008; 53(3):227-38. · 2.57 Impact Factor
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ABSTRACT: ERCC1 (excision repair cross complementation group 1) is a subunit of the nucleotide excision repair complex, which can perform DNA strand incision correction of DNA damage. Association studies on the ERCC1 polymorphisms (C8092A and T19007C) in cancer had shown conflicting results. We performed a meta-analysis from all eligible case-control studies to assess the purported associations. Overall, the 19007C allele (3 853 patients and 4 349 controls) showed no significant effect on cancer risk compared to 19007T allele (P=0.39, odds ratio (OR)=0.95; 95% confidence interval (CI) 0.85-1.06, P(heterogeneity)=0.001) in all subjects. Meta-analysis under other genetic contrasts did not reveal any significant association of T19007C to cancer in all subjects, Caucasians and Asians. The 19007C allele (2 279 patients and 2 808 controls) showed no significant effect on lung cancer risk compared to 19007T allele (P=0.72, OR=0.94, 95% CI 0.69-1.29, P(heterogeneity)=0.0001) in all subjects. No significant effect of 8092A allele (3 865 patients and 3 750 controls) on cancer risk in all subjects (P=0.85, OR=1.01, 95% CI 0.94-1.08, P(heterogeneity)=0.92) and in Caucasians and Asians compare to 8092C. No evidences of association of C8092A (501 patients and 620 controls) to squamous cell carcinoma were found. The accumulated evidence indicated ERCC1 T19007C and C8092A might not be risk factors for cancer. Significant between-study heterogeneity existed in T19007C, which arose from a study showing significant protecting effect of 19007C allele compare to 19007T allele in smokers. More studies based on larger, stratified case-control population should be required to further evaluate the role of ERCC1 C8092A and T19007C polymorphisms in different cancer, especially in smokers.
European Journal of HumanGenetics 10/2007; 15(9):967-73. · 4.40 Impact Factor
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Liyun Sun,
Shengdong Huang, Qihan Wu,
Shaohua Gu,
Xuping Fu,
Ke Yu,
Fanglin Lu,
Chaoneng Ji,
Congjing Feng,
Ruping Sun,
Yi Xie,
Yumin Mao
[show abstract]
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ABSTRACT: In an effort to better understand the transcriptional program regulated by transcription factor, AP-2delta, we used cDNA microarray to evaluate the relative expression of human genes in AD293 cells by exogenous expression of AP-2delta. Microarray showed 29 genes that were up-regulated and 39 genes with a down-regulated expression pattern. Among the identified genes were those encoding transcription factors, signal transduction molecules, kinases, as well as genes regulating cell growth, differentiation, and cell adhesion, a set of genes suggested to be regulated by AP-2. The results of microarray was validated for some regulated genes by real-time PCR analysis. These observations shed novel insight into the mechanism of AP-2delta action and provide a range of target genes for further investigation.
Frontiers in Bioscience 02/2007; 12:1699-706. · 3.52 Impact Factor
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ABSTRACT: A novel member of human protein phosphatase 2C gene named PP2Ckappa was isolated from a human fetal brain cDNA library. The 2.0 kb cDNA encodes a 372 amino acid polypeptide with an intact protein phosphatase 2C (PP2C) catalytic domain. Reverse transcription-PCR (RT-PCR) revealed that the PP2Ckappa was widely expressed in normal human tissues. Transient transfection suggested that PP2Ckappa was localized in the nucleus in AD293 cells. Recombinant Trx-His-PP2Ckappa showed phosphatase activity toward p-nitrophenyl phosphate (pNPP), as well as oligopeptides containing phospho-threonine residues. Furthermore, the overexpression of PP2Ckappa distinctly activated the heat shock transcription factor pathway in eukaryotic cells.
International Journal of Molecular Medicine 07/2006; 17(6):1117-23. · 1.98 Impact Factor
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Qihan Wu,
Shengdong Huang,
Yaqiong Sun,
Shaohua Gu,
Fanglin Lu,
Jianfeng Dai,
Gang Yin,
Liyun Sun,
Dan Zheng,
Chao Dou,
Congjing Feng,
Chaoneng Ji,
Yi Xie,
Yumin Mao
[show abstract]
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ABSTRACT: The SAPK/JNKs play important roles in numerous cellular processes, and for this reason they have become putative drug targets. Most dual-specificity protein phosphatases (DSPs) play important roles in the regulation of mitogenic signal transduction and cell cycle control in response to extracellular stimuli. Dual-specificity phosphatase 18 (DUSP18), a newly recognized SAPK/JNK phosphatase, is widely expressed. This expression is modulated in response to extracellular stimuli. By phosphorylation assay, pull down and coimmunoprecipitation experiments, it is shown here that DUSP18 interacts with SAPK/JNK and dephosphorylates it both in vitro and in vivo. DUSP18 does not dephosphorylate p38 or p44ERK1. Furthermore, DUSP18 inhibits SAPK/JNK pathway in vivo. Based on these findings, DUSP18 appears to serve an important role by regulation of SAPK/JNK pathway.
Frontiers in Bioscience 02/2006; 11:2714-24. · 3.52 Impact Factor
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Liyun Sun,
Shaohua Gu,
Yaqiong Sun,
Dan Zheng, Qihan Wu,
Xin Li,
Jianfeng Dai,
Jianliang Dai,
Chaoneng Ji,
Yi Xie,
Yumin Mao
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ABSTRACT: This study reports the cloning and characterization of a novel human phosphatidic acid phosphatase type 2 isoform cDNAs (PAP2d) from the foetal brain cDNA library. The PAP2d gene is localized on chromosome 1p21.3. It contains six exons and spans 112 kb of the genomic DNA. By large-scale cDNA sequencing we found two splice variants of PAP2d, PAP2d_v1 and PAP2d_v2. The PAP2d_v1 cDNA is 1722 bp in length and spans an open reading frame from nucleotide 56 to 1021, encoding a 321aa protein. The PAP2d_v2 cDNA is 1707 bp in length encoding a 316aa protein from nucleotide 56-1006. The PAP2d_v1 cDNA is 15 bp longer than the PAP2d_v2 cDNA in the terminal of the fifth exon and it creates different ORF. Both of the proteins contain a well-conserved PAP2 motif. The PAP2d_v1 is mainly expressed in human brain, lung, kidney, testis and colon, while PAP2d_v2 is restricted to human placenta, skeletal muscle, and kidney. The two splice variants are co-expressed only in kidney.
Molecular and Cellular Biochemistry 05/2005; 272(1-2):91-6. · 2.06 Impact Factor
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Liu Wang,
Chaoneng Jil,
Yiren Xu,
Jian Xu,
Jianfeng Dai, Qihan Wu,
Maoqing Wu,
Xianqiong Zou,
Liyun Sun,
Shaohua Gu,
Yi Xie,
Yumin Mao
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ABSTRACT: Mouse U26 has been defined as a 2-aminoadipic 6-semialdehyde dehydrogenase. It was speculated to be a PQQ-dependent AAS dehydrogenase due to the research of demonstrating PQQ as a new B vitamin. We isolated a novel human cDNA from the human fetal brain cDNA library we constructed. Its deduced protein was most related to mouse U26. Thus, we termed it human U26. This putative protein contains an AMP-binding domain, a Phosphopantetheine-binding domain and six PQQ-binding motifs. Human U26 mRNA is ubiquitously expressed in adult tissues and is highly expressed in colon adenocarcinoma (CX-1) and colon adenocarcinoma (GI-112) cell lines. Further study should be made to clarify the precise function of human U26.
Molecular Biology Reports 04/2005; 32(1):47-53. · 2.93 Impact Factor
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ABSTRACT: Most of dual-specificity protein phosphatases (DSPs) play an important role in the regulation of mitogenic signal transduction and controlling the cell cycle in response to extracellular stimuli. In this study, a novel human dual-specificity protein phosphatases gene named dual-specificity phosphatase 23 (DUSP23) was isolated by large-scale sequencing analysis of a human fetal brain cDNA library. Its cDNA was 726 bp in length, encoding a 150-amino acid polypeptide which contained a dual-specificity phosphatase catalytic (DSPc) domain but not a CDC25 homology (CH2) domain. Reverse transcription-PCR (RT-PCR) revealed that the DUSP23 was expressed in most fetal tissues and two adult tissues: testis and colon. Transient transfection experiment suggested that DUSP23 was localized in the cytoplasm of HEK293 cells. DUSP23 showed distinctive phosphatase activity toward p-nitrophenyl phosphate (pNPP), as well as oligopeptides containing phospho-tyrosine and phospho-threonine residues. Furthermore, DUSP23 could dephosphorylate p44ERK1 but not p38 and p54SAPKbeta in vitro. All the results indicated that DUSP23 was a novel protein phosphatase with dual substrate specificity.
The International Journal of Biochemistry & Cell Biology 09/2004; 36(8):1542-53. · 4.63 Impact Factor
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Jian Xu,
Ti He,
Liu Wang, Qihan Wu,
Enpeng Zhao,
Maoqing Wu,
Tonghai Dou,
Chaoneng Ji,
Shaohua Gu,
Kang Yin,
Yi Xie,
Yumin Mao
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ABSTRACT: BTB/POZ domain is an evolutionarily conserved protein-protein interaction domain often found in developmentally regulated transcription factors. Previous studies have shown that many additional conserved motifs have been found in association with BTB/POZ domain, including kelch repeats, zinc finger domains, FYVE fingers and ankyrin repeats. Here we report a novel human gene containing double BTB/POZ domains, named BTBD8 in agreement with the HUGO Nomenclature Committee. The cDNA sequence contains an open reading frame of 918 bp encoding a putative protein of 305 amino acid residues with a predicted molecular mass of 34.6 kDa. Protein pattern analysis shows that it contains double BTB/POZ domains. Weak expression was detected in adult brain and prostate of the 16 adult tissues examined, while it had a more abundant expression pattern in human fetal brain. The expression pattern of BTBD8 shows it may have a function related to brain development.
International Journal of Molecular Medicine 02/2004; 13(1):193-7. · 1.98 Impact Factor
