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Biomedical subjects

Yumin Mao

Publications and source records attributed to Yumin Mao.

At least 19 recordsLinked to original sources
PubMed2006

Different gene expression profiles of AD293 and HEK293 cell lines that show contrasting susceptibility to apoptosis induced by overexpression of Bim L.

Bim is a pro-apoptotic member of the Bcl-2 protein family. Overexpression of Bim proved to be highly cytotoxic for diverse cells. The AD293 cell line is derived directly from the HEK293 cell line but has been transfected with a gene that can improve cell adherence. We found that there was almost no apoptosis seen in Bim L-transfected AD293 cells, but more than half of Bim L-transfected HEK293 cells underwent apoptosis. Suppression subtractive hybridization was used to detect the different gene expression profile between these two cell lines. In 192 sequenced positive clones, there were 30 clones repeating twice or more. Ten genes were selected for identification by semi-quantitative RT-PCR. The transcripts of two adhesion-related genes (actin and parvin) and two apoptosis-related genes (cyclin 2 and protein phosphatase 1G) were up-regulated in AD293 cells. These results suggest that the high expression of cell adhesion-related proteins might be responsible for the different apoptosis status after the transfection of Bim L. Our data provide candidate genes responsible for the different apoptosis sensitivity of these two cell lines. Further investigation on the differential expression profile between AD293 and HEK293 might improve our understanding of cell apoptosis mechanism.

Actins↗
PubMed2006

Dual specificity phosphotase 18, interacting with SAPK, dephosphorylates SAPK and inhibits SAPK/JNK signal pathway in vivo.

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.

Blotting, Western↗
PubMed2006

Application of HLA-DRB1 genotyping by oligonucleotide micro-array technology in forensic medicine.

UNLABELLED: The human leukocyte antigen (HLA) system is known to be the most complex polymorphic system in the human genome. Among all of the HLA loci, HLA-DRB1 has the second largest number of alleles. The purpose of this study is to develop an oligonucleotide micro-array based HLA-DRB1 typing system for use in forensic identification, anthropology, tissue transplantation, and other genetic research fields. The system was developed by analyzing the HLA-DRB1 (DRB1) genotypes in 1198 unrelated healthy Chinese Han individuals originating from various parts of China and residing in Shanghai, China. METHOD: Polymerase chain reaction (PCR) coupled with the oligonucleotide micro-array technology was used to detect and type HLA-DRB1 alleles of the sample individuals. The reliability, sensitivity, consistency and specificity were evaluated for use in forensic identification. Furthermore, a meta-analysis was carried out by comparing the allele frequencies of the HLA-DRB1 locus with those of other Chinese Han groups, Chinese minorities and other ethnic populations. RESULTS: All the DNA samples yielded a 273 bp amplification product, with no other amplification products in this length range. The minimum quantity of DNA detected by this method is 15 ng in a PCR reaction system of 25 microl. The population studied appeared to be not in Hardy-Weinberg equilibrium. Observed heterozygosity (Ho), expected heterozygosity (He), expected probability of exclusion (PE), polymorphic information content (PIC), and discrimination power (DP) of the HLA-DRB1 locus from the Shanghai Han ethnic group were evaluated to be 0.8022, 0.8870, 0.7741, 0.8771, 0.9750, respectively. A total of 25 HLA-DRB1 alleles were identified. HLA-DRB1*09XX, *04XX, *12XX and *15XX were the most frequent DRB1 alleles, which were observed in 58.76% of the sample. One hundred and sixteen genotypes were found. The five most frequent genotypes were: *04XX/*04XX (0.0626), *09XX/*09XX (0.0593), *04XX/*09XX (0.0551), *09XX/*15XX (0.0384) and *08XX/*12XX (0.0351). The meta-analysis showed that there were uniquely distributed features of DRB1 alleles among various ethnic populations and among the studied population groups from various regions with the same ethnic origin. CONCLUSIONS: An HLA-DRB1 genotyping system has been developed and established based on the oligonucleotide micro-array technology. The HLA-DRB1 typing of the Han population in Shanghai has revealed a relatively high heterogeneity. Information obtained in this study will be useful for medical and forensic applications as well as in anthropology research. Large-scale micro-array detection is highly accurate and reliable for DNA-based HLA-DRB1 genotyping. These results suggest that HLA-DRB1 DNA polymorphisms and the database of the Shanghai Han group have useful applications in processing forensic casework (as personal identification, paternity test), tracing population migration and genetic diagnosis.

Animals↗
PubMed2006

DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies.

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. However, association studies on the XRCC3 polymorphisms (4541A>G, Thr(241)Met, 17893A>G) in cancer have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported associations. Forty eight eligible case-control studies including 24,975 cancer patients and 34, 209 controls were selected for our meta-analysis. Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer risk under a recessive genetic model. The subgroup and meta-regression analysis demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in cancer susceptibility for different subgroups. Specially, there was a significantly increased risk of breast cancer (OR, 1.14; P=0.0004; 95% CI, 1.06-1.23; P=0.37 for heterogeneity), elevated but not significant risk of cancer for head and neck, bladder, surprisingly, a significantly decreased risk of non-melanoma skin cancer (OR, 0.76; P=0.007; 95% CI, 0.62-0.93; P=0.61 for heterogeneity). A significantly elevated risk of cancer was observed in population-based case-control studies but not in nested or hospital based studies. Similarly, we found a significantly increased risk of cancer for A4541G and a decreased risk for A17893G under dominant genetic models. Our meta-analysis results support that the XRCC3 might represent a low-penetrance susceptible gene especially for cancer of breast, bladder, head and neck, and non-melanoma skin cancer. A single larger study should be required to further evaluate gene-gene and gene-environment interactions on XRCC3 polymorphisms and tissue-specific cancer risk in an ethnicity specific population.

Amino Acid Substitution↗
PubMed2006

CTLA4 polymorphisms and ophthalmopathy in Graves' disease patients: association study and meta-analysis.

Studies in the past have clearly established that cytotoxic T-lymphocyte antigen-4 (CTLA4) is a susceptible gene for Graves' disease (GD). However, association studies between the CTLA4 exon-1 +49A/G polymorphism and the risk of developing Graves' ophthalmopathy (GO) in GD patients have revealed conflicting results. In this study, associations of two CTLA4 polymorphisms (+49A/G and CT60) with GD risk and GO susceptibility in GD patients were investigated in a Chinese population. In addition, a meta-analysis was performed to better assess the purported association between the +49A/G polymorphism and GO susceptibility in GD patients. Our results demonstrated that both the +49A/G and CT60 polymorphisms were associated with GD susceptibility in the Chinese population. No significant association with GO susceptibility in GD patients was confirmed regardless of which polymorphism was tested individually. Similarly, the meta-analysis results provided minimal evidence about the role of the +49A/G polymorphism and GO risk in GD patients. Interestingly, haplotypic analysis demonstrated different scenarios concerning the role of CTLA4 in GO susceptibility in the Chinese GD patients. We found that the +49A-CT60G haplotype was marginally statistically associated with the increased risk of GO in GD patients (OR = 1.63, 95%CI 1.00-2.64, p = 0.05). In conclusion, our results suggested that CTLA4 might be involved in the susceptibility to GD in the Chinese population. Although neither +49A/G nor CT60 polymorphism was associated with the risk of GO in GD patients, the haplotypic analysis provided some evidence about its role in GO susceptibility in the Chinese GD patients. We suggest that more association studies recruiting haplotypic analysis should be performed to investigate the role of CTLA4 gene in GO susceptibility in patients from different nations.

Adult↗
PubMed2006

Cloning, characterization and subcellular localization of a gene encoding a human Ubiquitin-conjugating enzyme (E2) homologous to the Arabidopsis thaliana UBC-16 gene product.

Ubiquitin charging and activation of class III E2 enzymes has been directly linked to their nuclear import. It has not been published whether other classes E2s also abide by this mechanism. During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a cDNA clone that is 2252 base pair in length, encoding a putative 162 amino acid protein, which shares high homology to Arabidopsis thaliana ubiquitin-conjugating enzyme 16 (Accession number NP_565110, 51% identity and 71% similarity) at protein level. Bioinformatics analysis revealed that the gene is composed of 7 exons, located on human chromosome 8q13-8q21.1, and that the predicted protein of the gene is a class I E2, for only composed of a conserved approximately 150-amino acid catalytic core, ubiquitin-conjugating enzyme E2 domain (UBC domain). In the C-terminal of the UBC domain sequence, there are two nuclear localization signals (NLSs). RT-PCR showed that this gene is ubiquitously expressed in 16 kinds of normal human tissues, but expression level is very low, unless in human heart, brain, liver, and pancreas. The subcellular localizations of the new human Ubiquitin conjugating enzyme E2 and its mutation were also examined, which showed that the nuclear localization of hUBC16 depended on two conditions: It has NLS, and at the same time, has enzyme active site, too, at least in HEK293 cells.

Amino Acid Sequence↗
PubMed2006

Crystal structures of human glycerol 3-phosphate dehydrogenase 1 (GPD1).

Homo sapiens L-alpha-glycerol-3-phosphate dehydrogenase 1 (GPD1) catalyzes the reversible biological conversion of dihydroxyacetone (DHAP) to glycerol-3-phosphate. The GPD1 protein was expressed in Escherichia coli, and purified as a fusion protein with glutathione S-transferase. Here we report the apoenzyme structure of GPD1 determined by multiwavelength anomalous diffraction phasing, and other complex structures with small molecules (NAD+ and DHAP) by the molecular replacement method. This enzyme structure is organized into two distinct domains, the N-terminal eight-stranded beta-sheet sandwich domain and the C-terminal helical substrate-binding domain. An electrophilic catalytic mechanism by the epsilon-NH3+ group of Lys204 is proposed on the basis of the structural analyses. In addition, the inhibitory effects of zinc and sulfate on GPDHs are assayed and discussed.

Catalysis↗
PubMed2006

Co-evolutionary analysis of insulin/insulin like growth factor 1 signal pathway in vertebrate species.

Insulin/insulin like growth factor 1 signaling pathway plays an essential role on the regulation of variant, interrelated and fundamental processes, such as metabolism, growth, reproduction and aging. This pathway is highly conserved during evolution. We analyzed eight vertebrate species' insulin/insulin like growth factor 1 pathway and examined the co-evolutionary relationship between different protein components by quantifying similarity of phylogenetic trees. The collected species include Takifugu rubripes, Danio rerio, Xenopus laevis, Gallus gallus, Mus musculus, Rattous norvegicus, Pan troglodytes and Homo sapiens. Results show that interacting proteins in this pathway share highly co-evolutionary relationship while contrarily the proteins without interaction have low co-evolutionary relationship. We also predict some receptor and ligand partners enjoy highly binding potential in corresponding species' pathway.

Animals↗
PubMed2006

Genes differentially expressed in responsive and refractory acute leukemia.

DNA microarray in 22 patients with acute leukemia revealed genes which were differentially expressed. Ribosomal protein SA (RPSA), minichromosome maintenance deficient 2 (MCM2) and heterogeneous nuclear ribonucleoprotein A1 (HNRPA1) were significantly upregulated (p<0.05, t test) in refractory patients, suggesting that they may play a role in refractoriness in acute leukemia and could be biomarkers of prognosis.

Adolescent↗
PubMed2006

Cloning and characterization of a novel KRAB-domain-containing zinc finger gene (ZNF284L).

The zinc finger gene (ZNF) family plays an important role in the regulation of transcription. This study reports the cloning and characterization of a novel human zinc finger protein cDNA (ZNF284L) from fetal brain cDNA library. The ZNF284L cDNA is 2223 bp in length encoding a 593-aa polypeptide. The protein contains a KRAB A+b box and eleven C2H2 type zinc finger motifs. ZNF284L gene is mapped to 19q13.2-19q13.3 with 5 exons, and the expression pattern of ZNF284L gene was also examined by reverse transcription polymerase chain reaction (RT-PCR). The transcripts were detected in the human lung, liver, pancreas, thymus, heart, placenta, spleen, prostate, ovary, small intestine and colon, but in human brain, skeletal muscle, kidney, testis and peripheral blood leukocyte, no expression was detected.

Amino Acid Sequence↗
PubMed2006

Human RAB24, interestingly and predominantly distributed in the nuclei of COS-7 cells, is colocalized with cyclophilin A and GABARAP.

As an atypical member of the Rab family, Rab24 has several attributes distinguishing this protein from the other members. Based on the yeast two-hybrid system, interaction between human RAB24 and two proteins, cyclophilin A (CyP-A) and gamma-aminobutyric acid type A receptor-associated protein (GABARAP), was detected and identified in COS-7 cells. Interestingly, RAB24 is predominantly localized in the nuclei of COS-7 cells, which is different from previous reports using other cell lines. RAB24 (D123I) can trigger the accumulation of intracellular inclusions, with small quantities of intranuclear inclusions in some cells. The GTPase activity of RAB24 and its two mutants was detected.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Characterization of a novel human protein phosphatase 2C family member, PP2Ckappa.

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.

Amino Acid Sequence↗
PubMed2005

Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP.

Guanosine monophosphate reductase (GMPR) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP, and plays a critical role in re-utilization of free intracellular bases and purine nucleosides. Here, we report the first crystal structure of human GMP reductase 2 (hGMPR2) in complex with GMP at 3.0 A resolution. The protein forms a tetramer composed of subunits adopting the ubiquitous (alpha/beta)8 barrel fold. Interestingly, the substrate GMP is bound to hGMPR2 through interactions with Met269, Ser270, Arg286, Ser288, and Gly290; this makes the conformation of the adjacent flexible binding region (residues 268-289) fixed, much like a door on a hinge. Structure comparison and sequence alignment analyses show that the conformation of the active site loop (residues 179-187) is similar to those of hGMPR1 and inosine monophosphate dehydrogenases (IMPDHs). We propose that Cys186 is the potential active site, and that the conformation of the loop (residues 129-133) suggests a preference for the coenzyme NADPH over NADH. This structure provides important information towards understanding the functions of members of the GMPR family.

Amino Acid Sequence↗
PubMed2005

Identification and characterization of a novel Cut family cDNA that encodes human copper transporter protein CutC.

Copper is an essential heavy metal trace element that plays important roles in cell physiology. The Cut family was associated with the copper homeostasis and involved in several important metabolisms, such as uptake, storage, delivery, and efflux of copper. In this study, a novel Cut family cDNA was isolated from the human fetal brain library, which encodes a 273 amino acid protein with a molecular mass of about 29.3 kDa and a calculated pI of 8.17. It was named hCutC (human copper transporter protein CutC). The ORF of hCutC gene was cloned into pQE30 vector and expressed in Escherichia coli M15. The secreted hCutC protein was purified to a homogenicity of 95% by using the Ni-NTA affinity chromatography. RT-PCR analysis showed that the hCutC gene expressed extensively in human tissues. Subcellular location analysis of hCutC-EGFP fusion protein revealed that hCutC was distributed to cytoplasm of COS-7 cells, and both cytoplasm and nucleus of AD293 cells. The results suggest that hCutC may be one shuttle protein and play important roles in intracellular copper trafficking.

Amino Acid Sequence↗
PubMed2005

Isolation and expression pattern of RGS21 gene, a novel RGS member.

Regulators of G-protein signaling (RGS) proteins are known for the RGS domain that is composed of a conserved stretch of 120 amino acids, which binds directly to activated G-protein alpha subunits and acts as a GTPase-activating protein (GAP), leading to their deactivation and termination of downstream signals. In this study, a novel human RGS cDNA (RGS21), 1795 bp long and encoding a 152-amino acid polypeptide, was isolated by large-scale sequencing analysis of a human fetal brain cDNA library. Unlike other RGS family members, RGS21 gene has no additional domain/motif and may represent the smallest known member of RGS family. It may belong to the B/R4 subfamily, which suggests that it may serve exclusively as a negative regulator of alphai/o family members and/or alphaq/11. PCR analysis showed that RGS21 mRNA was expressed ubiquitously in the 16 tissues examined, implying general physiological roles.

Amino Acid Sequence↗
PubMed2005

Finding dominant sets in microarray data.

Clustering allows us to extract groups of genes that are tightly coexpressed from Microarray data. In this paper, a new method DSF_Clust is developed to find dominant sets (clusters). We have preformed DSF_Clust on several gene expression datasets and given the evaluation with some criteria. The results showed that this approach could cluster dominant sets of good quality compared to kmeans method. DSF_Clust deals with three issues that have bedeviled clustering, some dominant sets being statistically determined in a significance level, predefining cluster structure being not required, and the quality of a dominant set being ensured. We have also applied this approach to analyze published data of yeast cell cycle gene expression and found some biologically meaningful gene groups to be dug out. Furthermore, DSF_Clust is a potentially good tool to search for putative regulatory signals.

Algorithms↗
PubMed2005

Meta-analysis of the association of CTLA-4 exon-1 +49A/G polymorphism with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a highly suspected candidate gene for RA susceptibility. However, association studies on the polymorphism of CTLA-4 exon-1 +49A/G in RA have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported association. In order to look for ethnic effect, we performed subgroup meta-analysis in populations of European descent and Asian descent. Meta-regression analysis was also performed to explore the possible heterogeneity between the two subgroups. Ten studies (11 comparisons) with the CTLA-4 exon-1 +49A/G genotyping on 2,315 patients with RA and 2,536 controls were selected for our meta-analysis. Overall, the fixed-effects odds ratio (OR) for the G versus A allele was 1.11 (P=0.02, 95% confidence interval (CI) 1.02-1.21), with no between-study heterogeneity. Subgroup and meta-regression analysis according to the ethnicity (European or Asian) demonstrated different scenarios concerning the CTLA-4 exon-1 +49A/G polymorphism's role in RA susceptibility for the two different subgroups. No effect of G on susceptibility was seen in European descent (five comparisons; OR=1.04, P=0.30, 95% CI 0.95-1.19; no significant between-study heterogeneity). However, there is a significant association in Asian descent under both fixed [OR=1.21, 95% CI (1.06-1.39), P=0.005] and random-effect models [OR=1.19, 95% CI (1.01-1.42), P=0.04]. Meta-regression analysis also supports the heterogeneity between the two subgroups (P=0.082). We also explored the role of this polymorphism on RA risk under other various interested genetic contrasts. These results further support that this polymorphism could not be a risk factor for Europeans. Interestingly, we find that in Asians the G allele has a greater tendency to cause RA in a recessive genetic model. However, sensitivity analysis showed that the combined result of Asian populations was unstable. In conclusion, our meta-analysis results suggest that CTLA-4 exon-1 +49G allele would not be a risk factor for RA in Europeans but might play a role in RA susceptibility for Asians.

Alleles↗