共查询到20条相似文献,搜索用时 31 毫秒
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Roland Wicki Ingo Marenholz Dietmar Mischke Beat W. Schäfer Claus W. Heizmann 《Cell calcium》1996,20(6):459-464
Here, we report the characterization of a human cDNA coding for the recently published amino acid sequence of a calcium-binding S100 protein, S100A12 (CGRP, calgranulin C, CAAF1, p6). The exon/intron structure of the S100A12 gene is similar to most other S100 genes. It is composed of three exons which are divided by two introns of 900 by and 400 bp. The protein is encoded by sequences in exons 2 and 3, with exon 2 coding for the N-terminal 45 amino acids and exon 3 coding for the C-terminal 46 amino acids. So far, ten S100 genes are known to be located on human chromosome 1q21 in a clustered organization. Hence, we investigated whether S100A11 (S1000, calgizzarin) and S100A12 are also localized in the S100 gene cluster. We found both genes within the cluster, with S100A11 being close to S100A10 and S100A12 between the genes S100A8 and S100A9. Therefore, the S100 gene cluster now is composed of 12 differentially expressed family members. 相似文献
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Xuanfu Xu Bin Su Chuangao Xie Shumei Wei Yingqun Zhou Hua Liu Weiqi Dai Ping Cheng Fan Wang Xiaorong Xu Chuanyong Guo 《PloS one》2014,9(7)
Aims
The hedgehog signaling pathway plays an important role in EMT of pancreatic cancer cells, but the precise mechanisms remain elusive. Because S100A4 as a key EMT moleculer marker was found to be upregulated upon Gli1 in pancreatic cancer cells, we focused on the relationship between Shh-Gli1 signals and S100 genes family.Methods
On the base of cDNA microarray data, we investigated regulating mechanism of Gli1 to some members of S100A genes family in pancreatic cancer cell lines firstly. Then, the regulation of Gli1 to S100A4 gene was studied by molecular biology assays and the pro-metastasis effection of Gli1-dependent S100A4 was investigated in vitro. Finally, the expressions of Shh, Gli1, S100A4 and E-cadherin in pancreatic cancer tissues were studied by using immunohistochemistry assays.Results
Five members of the S100 genes family, S100A2, S100A4, S100A6, S100A11, and S100A14 were found to be downregulated significantly upon Gli1 knockdown. Gli1 enhancer prediction combining with in vitro data demonstrated that Gli1 primarily regulates S100A family members via cis-acting elements. Indeed, the data indicate S100A4 and vimentin genes were upregulated significantly by Shh/Gli1-expression increasing and E-cadherin was significantly reduced at the same time. Migration of PC cells was increased significantly in a dose-dependent manner of Gli1 expression (P<0.05) and siS100A4 significantly reversed the response of PC cells induced by L-Shh transduction (P<0.01).Conclusion
Our data establish a novel connection between Shh-Gli1 signaling and S100A4 regulation, which imply that S100A4 might be one of the key factors in EMT mediated by Shh-Gli1 signaling in pancreatic cancer. 相似文献5.
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The interaction of the Ca2+-binding protein S100A12 with RAGE (receptor of advanced glycation endproducts) has been considered as a novel proinflammatory axis, since blockage of RAGE/S100A12 ligation suppresses chronic cellular activation and tissue injury in mouse models. However, the existence of a murine S100A12 ortholog is unknown. Because experimental approaches failed to identify it, we started an analysis of gene locus evolution. Human S100A12 is localized in the S100 gene cluster between S100A8 and S100A9, which are neighbors in both mouse and human. Confirming identical gene order, we found a DNA region between the murine S100A8 and S100A9 genes that is 60.9% identical to a region of the human S100A12 gene, including the first exon. Instead of the second and third exon, we found homology to a region close to the human S100A9 locus. To exclude a murine S100A12 ortholog elsewhere in the genome, we used human S100A12 as query for TBlastN homology searches. The matches were either too short, or identity was too low, or they could clearly be identified as distinct S100 genes. Obviously, an S100A12 ortholog is neither present in mouse nor rat, indicating that S100A12 has been lost during rodent evolution, probably due to a deletion. 相似文献
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Na Chen Daisuke Sato Yuriko Saiki Makoto SunamuraShinichi Fukushige Akira Horii 《Biochemical and biophysical research communications》2014
S100A4, a small calcium-binding protein belonging to the S100 protein family, is commonly overexpressed in a variety of tumor types and is widely accepted to associate with metastasis by regulating the motility and invasiveness of cancer cells. However, its biological role in lung carcinogenesis is largely unknown. In this study, we found that S100A4 was frequently overexpressed in lung cancer cells, irrespective of histological subtype. Then we performed knockdown and forced expression of S100A4 in lung cancer cell lines and found that specific knockdown of S100A4 effectively suppressed cell proliferation only in lung cancer cells with S100A4-overexpression; forced expression of S100A4 accelerated cell motility only in S100A4 low-expressing lung cancer cells. PRDM2 and VASH1, identified as novel upregulated genes by microarray after specific knockdown of S100A4 in pancreatic cancer, were also analyzed, and we found that PRDM2 was significantly upregulated after S100A4-knockdown in one of two analyzed S100A4-overexpressing lung cancer cells. Our present results suggest that S100A4 plays an important role in lung carcinogenesis by means of cell proliferation and motility by a pathway similar to that in pancreatic cancer. 相似文献
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The tumor microenvironment plays an important role in modulating tumor progression. Earlier, we showed that S100A8/A9 proteins secreted by myeloid-derived suppressor cells (MDSC) present within tumors and metastatic sites promote an autocrine pathway for accumulation of MDSC. In a mouse model of colitis-associated colon cancer, we also showed that S100A8/A9-positive cells accumulate in all regions of dysplasia and adenoma. Here we present evidence that S100A8/A9 interact with RAGE and carboxylated glycans on colon tumor cells and promote activation of MAPK and NF-κB signaling pathways. Comparison of gene expression profiles of S100A8/A9-activated colon tumor cells versus unactivated cells led us to identify a small cohort of genes upregulated in activated cells, including Cxcl1, Ccl5 and Ccl7, Slc39a10, Lcn2, Zc3h12a, Enpp2, and other genes, whose products promote leukocyte recruitment, angiogenesis, tumor migration, wound healing, and formation of premetastatic niches in distal metastatic organs. Consistent with this observation, in murine colon tumor models we found that chemokines were upregulated in tumors, and elevated in sera of tumor-bearing wild-type mice. Mice lacking S100A9 showed significantly reduced tumor incidence, growth and metastasis, reduced chemokine levels, and reduced infiltration of CD11b(+)Gr1(+) cells within tumors and premetastatic organs. Studies using bone marrow chimeric mice revealed that S100A8/A9 expression on myeloid cells is essential for development of colon tumors. Our results thus reveal a novel role for myeloid-derived S100A8/A9 in activating specific downstream genes associated with tumorigenesis and in promoting tumor growth and metastasis. 相似文献
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Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+ -ATPase2a and phospholamban in the human heart 总被引:4,自引:0,他引:4
Kiewitz R Acklin C Schäfer BW Maco B Uhrík B Wuytack F Erne P Heizmann CW 《Biochemical and biophysical research communications》2003,306(2):550-557
The Ca(2+)-binding S100A1 protein displays a specific and high expression level in the human myocardium and is considered to be an important regulator of heart contractility. Diminished protein levels detected in dilated cardiomyopathy possibly contribute to impaired Ca(2+) handling and contractility in heart failure. To elucidate the S100A1 signaling pathway in the human heart, we searched for S100A1 target proteins by applying S100A1-specific affinity chromatography and immunoprecipitation techniques. We detected the formation of a Ca(2+)-dependent complex of S100A1 with SERCA2a and PLB in the human myocardium. Using confocal laser scanning microscopy, we showed that all three proteins co-localize at the level of the SR in primary mouse cardiomyocytes and confirmed these results by immunoelectron microscopy in human biopsies. Our results support a regulatory role of S100A1 in the contraction-relaxation cycle in the human heart. 相似文献
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Jie Liang Guanhong Luo Xiaoxuan Ning Yongquan Shi Huihong Zhai Shiren Sun Haifeng Jin Zhenxiong Liu Faming Zhang Yuanyuan Lu Yunping Zhao Xiong Chen Hongbo Zhang Xuegang Guo Kaichun Wu Daiming Fan 《Biochimie et biologie cellulaire》2007,85(3):375-383
The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies, which causes prion disorders partially due to Ca2+ dysregulation. In our previous work, we found that overexpressed PrPC in gastric cancer was involved in apoptosis, cell proliferation, and metastasis of gastric cancer. To better understand how PrPC acts in gastric cancer, a human microarray was performed to select differentially regulated genes that correlate with the biological function of PrPC. The microarray data were analyzed and revealed 3798 genes whose expression increased at least 2-fold in gastric cancer cells transfected with PrPC. These genes encode proteins involved in several aspects of cell biology, among which, we specially detected molecules related to calcium, especially the S100 calcium-binding proteins, and found that PrPC upregulates S100A1, S100A6, S100B, and S100P but downregulates CacyBP in gastric cancer cells. We also found that intracellular Ca2+ levels in cells transfected with PrPC increased, whereas these levels decreased in knockdowns of these cells. Taken together, PrPC might increase intracellular Ca2+, partially through calcium-binding proteins, or PrPC might upregulate the expression of S100 proteins, partially through stimulating the intracellular calcium level in gastric cancer. Though the underlying mechanisms need further exploration, this study provides a new insight into the role of PrPC in gastric cancer and enriches our knowledge of prion protein. 相似文献
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Cloning and expression of the human S100 beta gene 总被引:4,自引:0,他引:4
R J Allore W C Friend D O'Hanlon K M Neilson R Baumal R J Dunn A Marks 《The Journal of biological chemistry》1990,265(26):15537-15543
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Abstract
The human S100 gene family encodes the EF-hand superfamily of calcium-binding proteins, with at least 14 family members clustered
relatively closely together on chromosome 1q21. We have analyzed the most recently available genomic sequence of the human
S100 gene cluster for evidence of tandem gene duplications during primate evolutionary history. The sequences obtained from
both GenBank and GoldenPath were analyzed in detail using various comparative sequence analysis tools. We found that of the
S100A genes clustered relatively closely together within a genomic region of 260 kb, only the S100A7 (psoriasin) gene region
showed evidence of recent duplications. The S100A7 gene duplicated region is composed of three distinct genomic regions, 33,
11, and 31 kb, respectively, that together harbor at least five identifiable S100A7-like genes. Regions 1 and 3 are in opposite
orientation to each other, but each region carries two S100A7-like genes separated by an 11-kb intergenic region (region 2)
that has only one S100A7-like gene, providing limited sequence resemblance to regions 1 and 3. The duplicated genomic regions
1 and 3 share a number of different retroelements including five Alu subfamily members that serve as molecular clocks. The
shared (paralogous) Alu S insertions suggest that regions 1 and 3 were probably duplicated during or after the phase of AluS
amplification some 30–40 mya. We used PCR to amplify an indel within intron 1 of the S100A7a and S100A7c genes that gave the
same two expected product sizes using 40 human DNA samples and 1 chimpanzee sample, therefore confirming the presence of the
region 1 and 3 duplication in these species. Comparative genomic analysis of the other S100 gene members shows no similarity
between intergenic regions, suggesting that they diverged long before the emergence of the primates. This view was supported
by the phylogenetic analysis of different human S100 proteins including the human S100A7 protein members. The S100A7 protein,
also known as psoriasin, has important functions as a mediator and regulator in skin differentiation and disease (psoriasis),
in breast cancer, and as a chemotactic factor for inflammatory cells. This is the first report of five copies of the S100A7
gene in the human genome, which may impact on our understanding of the possible dose effects of these genes in inflammation
and normal skin development and pathogenesis. 相似文献
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Reppel M Sasse P Piekorz R Tang M Roell W Duan Y Kletke A Hescheler J Nürnberg B Fleischmann BK 《The Journal of biological chemistry》2005,280(43):36019-36028
S100A1 is an EF-hand type Ca2+-binding protein with a muscle-specific expression pattern. The highest S100A1 protein levels are found in cardiomyocytes, and it is expressed already at day 8 in the heart during embryonic development. Since S100A1 is known to be involved in the regulation of Ca2+ homeostasis, we tested whether extracellular S100A1 plays a role in regulating the L-type Ca2+ current (I(Ca)) in ventricular cardiomyocytes. Murine embryonic (day 16.5 postcoitum) ventricular cardiomyocytes were incubated with S100A1 (0.001-10 microM) for different time periods (20 min to 48 h). I(Ca) density was found to be significantly increased as early as 20 min (from -10.8 +/- 1 pA/pF, n = 18, to -22.9 +/- 1.4 pA/pF; +112.5 +/- 13%, n = 9, p < 0.001) after the addition of S100A1 (1 microM). S100A1 also enhanced I(Ca) current density in neonatal rat cardiomyocytes. Fluorescence and capacitance measurements evidenced a fast translocation of rhodamine-coupled S100A1 from the extracellular space into cardiomyocytes. S100A1 treatment did not affect cAMP levels. However, protein kinase inhibitor, a blocker of cAMP-dependent protein kinase A (PKA), abolished the S100A1-induced enhancement of I(Ca). Accordingly, measurements of PKA activity yielded a significant increase in S100A1-treated cardiomyocytes. In vitro reconstitution assays further demonstrated that S100A1 enhanced PKA activity. We conclude that the Ca2+-binding protein S100A1 augments transsarcolemmal Ca2+ influx via an increase of PKA activity in ventricular cardiomyocytes and hence represents an important regulator of cardiac function. 相似文献
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Genomic organization of the S locus: Identification and characterization of genes in SLG/SRK region of S(9) haplotype of Brassica campestris (syn. rapa). 总被引:10,自引:0,他引:10
G Suzuki N Kai T Hirose K Fukui T Nishio S Takayama A Isogai M Watanabe K Hinata 《Genetics》1999,153(1):391-400
In Brassica, two self-incompatibility genes, encoding SLG (S locus glycoprotein) and SRK (S-receptor kinase), are located at the S locus and expressed in the stigma. Recent molecular analysis has revealed that the S locus is highly polymorphic and contains several genes, i.e., SLG, SRK, the as-yet-unidentified pollen S gene(s), and other linked genes. In the present study, we searched for expressed sequences in a 76-kb SLG/SRK region of the S(9) haplotype of Brassica campestris (syn. rapa) and identified 10 genes in addition to the four previously identified (SLG(9), SRK(9), SAE1, and SLL2) in this haplotype. This gene density (1 gene/5.4 kb) suggests that the S locus is embedded in a gene-rich region of the genome. The average G + C content in this region is 32.6%. An En/Spm-type transposon-like element was found downstream of SLG(9). Among the genes we identified that had not previously been found to be linked to the S locus were genes encoding a small cysteine-rich protein, a J-domain protein, and an antisilencing protein (ASF1) homologue. The small cysteine-rich protein was similar to a pollen coat protein, named PCP-A1, which had previously been shown to bind SLG. 相似文献
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Regulation of the S100 protein and GFAP genes is mediated by two common mechanisms in RT4 neuro-glial cell lines 总被引:3,自引:0,他引:3
RT4-AC cells express both neuronal and glial properties and undergo cell-type conversion in culture to three distinct derivatives, described as either neuronal-like or glial-like. A coordinate induction of glial fibrillary acidic protein (GFAP) and S100 protein and GFAP gene expression is coordinately induced by cAMP. In addition, for the first time we provide direct evidence that the ability to express both the S100 and GFAP genes is conserved with cell-type conversion to the glial derivative cell types, but is coordinately lost with conversion to the neuronal derivative cell types. These results make it highly likely that the GFAP and S100 genes are regulated by two common mechanisms in RT4-AC cells: (1) cAMP-mediated control of gene expression; and (2) a mechanism that allows these two genes to be coordinately expressed or not expressed as a consequence of cell-type conversion. 相似文献
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S100A6 (calcyclin) is a calcium binding protein with two EF‐hand structures expressed mostly in fibroblasts and epithelial cells. We have established a NIH 3T3 fibroblast cell line stably transfected with siRNA against S100A6 to examine the effect of S100A6 deficiency on non‐transformed cell physiology. We found that NIH 3T3 fibroblasts with decreased level of S100A6 manifested altered cell morphology and proliferated at a much slower pace than the control cells. Cell cycle analysis showed that a large population of these cells lost the ability to respond to serum and persisted in the G0/G1 phase. Furthermore, fibroblasts with diminished S100A6 level exhibited morphological changes and biochemical features of cellular senescence as revealed by β‐galactosidase and gelatinase assays. Also, S100A6 deficiency induced changes in the actin cytoskeleton and had a profound impact on cell adhesion and migration. Thus, we have shown that the S100A6 protein is involved in multiple aspects of fibroblast physiology and that its presence ensures normal fibroblast proliferation and function. J. Cell. Biochem. 109: 576–584, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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为研究多鳞(Sillago sihama)低氧诱导因子抑制因子-1(factor inhibiting hypoxia inducible factor 1, fih-1)在低氧胁迫后的表达机制, 实验通过PCR扩增技术克隆出多鳞fih-1基因cDNA全长1280 bp, 开放阅读框(ORF)1065 bp, 编码353个氨基酸, 具有JmjC保守结构域。多序列比对与聚类分析显示, 多鳞与大黄鱼和尖吻鲈的亲缘关系最近, 与哺乳动物、两栖类和禽类的亲缘关系较远。fih-1基因mRNA在多鳞多个组织中有不同表达, 在精巢、卵巢和肌肉中的表达水平最高, 在鳃、心脏和肝脏组织表达水平较高, 在脑组织的表达水平较低。实时荧光定量PCR分析fih-1基因在低氧胁迫处理前后鳃和心脏组织中mRNA的表达情况, 结果显示fih-1基因在两个组织均随低氧胁迫处理时间延长表达量显著升高 (P< 0.05)。研究表明fih-1基因在多鳞低氧信号传导通路中扮演重要角色, 为开展并解释多鳞低氧胁迫遗传机制提供候选基因。 相似文献
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Microarray analysis of brain RNA in mice with methylenetetrahydrofolate reductase deficiency and hyperhomocysteinemia 总被引:2,自引:0,他引:2
Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia, which is associated with increased risk for cardiovascular disease, stroke and possibly other neurological disorders. Microarray analysis of brain RNA from day 14 Mthfr(-/-) mice revealed several genes with altered expression. Expression changes in inositol 1,4,5-triphosphate receptor, type 1 (Itpr1), proteolipid protein (Plp), neurogenic differentiation factor 1 (Neurod1), S100 calcium binding protein A8 (S100a8), and methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) were confirmed by RT-PCR. We propose that neuronal damage by hyperhomocysteinemia may involve disruption of intracellular calcium. 相似文献