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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosome 1 reveals in region 1q21 a most remarkable density of genes that fulfill important functions in terminal differentiation of the human epidermis. These genes encode the cornified envelope precursors loricrin, involucrin, and small proline-rich proteins (SPRR1, SPRR2, and SPRR3), the intermediate filament-associated proteins profilaggrin and trichohyalin, and several S100A calcium-binding proteins. Extending and refining our previous physical map of 1q21 we have now mapped two additional S100A genes as well as the three SPRR subfamilies and resolved the arrangement of involucrin, SPRRs, and loricrin. All genes are linked within 1.9 Mbp of human genomic DNA in the order: S100A10, trichohyalin, profilaggrin, involucrin, SPRR3, SPRR1B, SPRR2A, loricrin, S100A9, S100A9, S100A8, S100A6. Colocalization of genes expressed late during maturation of epidermal cells together with genes encoding calcium-binding proteins is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Accounting for the close functional cooperation among these structurally and evolutionary related genes, we conclude that these loci constitute a gene complex, for which we propose the name epidermal differentiation complex.
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PMID:Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. 861 63

The epidermal differentiation complex (EDC) unites a remarkable number of structurally, functionally, and evolutionarily related genes that play an important role in terminal differentiation of the human epidermis. It is localized within 2.05 Mb of region q21 on human chromosome 1. We have identified and characterized 24 yeast artificial chromosome (YAC) clones by mapping individual EDC genes, sequence-tagged site (STS) markers (D1S305, D1S442, D1S498, D1S1664), and 10 new region-specific probes (D1S3619-D1S3628). Here we present a contig that covers about 6 Mb of 1q21 including the entire EDC. Fluorescence in situ hybridization on metaphase chromosomes with two YACs flanking the EDC determined its chromosomal orientation and established, in conjunction with physical mapping results, the following order of genes and STSs: 1cen-D1S442-D1S498-S100A10-THH-FLG- D1S1664-IVL-SPRR3-SPRR1-SPRR2-LOR- S100A9-S100A8-S100A7-S100A6-S100A5-S100 A4- S100A3-S100A2-S100A1-D1S305-1qtel. These integrated physical, cytogenetic, and genetic mapping data will be useful for linkage analyses of diseases associated with region 1q21 and for the identification of novel genes and regulatory elements in the EDC.
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PMID:Genetic analysis of the epidermal differentiation complex (EDC) on human chromosome 1q21: chromosomal orientation, new markers, and a 6-Mb YAC contig. 893 41

S100 Ca2+-binding proteins became of major interest because of their differential expression in tissues and their association with human diseases. Earlier studies showed that 13 S100 genes are located as a cluster on human chromosome 1q21. Since a number of mouse S 100 genes, such as S100A4 and S100A6, have been localized to a syntenic region on mouse chromosome 3, we investigated if the S100 gene cluster exists in mouse and is structurally conserved during evolution. First we identified the cDNA sequences of mouse S100A1, S100A3 and S100A5. Then we isolated a 490 kb mouse YAC clone which gives a specific signal by FISH most likely on chromosome 3. Hybridization studies with different mouse S100 cDNAs revealed that eight mouse S100 genes are arranged in a clustered organization similar to that in human. The linkage relationships between the genes S100A8-S100A9 and S100A3-S100A4-S100A5-S100A6 were conserved during divergence of human and mouse about 70 million years ago. However, the separation of the mouse S100 genes S100A1 and S100A13 in comparison to the human linkage group suggests rearrangement processes between human and mouse. Our data demonstrate that the S100 gene cluster is structurally conserved during evolution. Further studies on the genomic organization of the S100 genes including various species could generate new insights into gene regulatory processes and phylogenetic relationships.
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PMID:Clustered organization of S100 genes in human and mouse. 992 Apr 16

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>S100A12>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.
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PMID:S100 proteins in Corpora amylacea from normal human brain. 1083 26

Anal cancer originates from a peculiar histological region and provides a useful model for investigating alterations in proliferation and/or differentiation of neoplastic keratinocytes. Epidermal differentiation complex (EDC) genes, which form one of the major gene clusters in the human genome, are involved in the terminal differentiation of epithelial cells and in many instances have been implicated in epithelial tumours. We constructed a DNA macroarray capable of characterising the expression profiles of the entire EDC gene complex in normal mucosa and anal cancer biopsies of seven unrelated patients. Brain tissue and cultured keratinocytes were used as controls. All anal cancer samples showed expression profiles in which none of the EDC genes was silent, as evaluated by phosphor-imager analysis. Variance analysis showed significantly lower expression of SPRR2 with respect to SPRR1 or SPRR3, and significantly higher expression of S100A8 than of other S100A subfamily members. At hierarchical clustering analysis, the four basaloid anal cancer cases conglomerated in the top five positions. The macroarray method used by us provides the first demonstration of the expression profile of the EDC gene family in anal cancer, and is capable of producing significant information on the subgrouping of epithelial tumours such as anal cancer.
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PMID:Expression profile of epidermal differentiation complex genes in normal and anal cancer cells. 1171 81

Serial analysis of gene expression provides quantitative and comprehensive expression profiling in a given cell population. In our efforts to define the genes overexpressed in carcinoma of the stomach, we performed serial analysis of gene expression analyses on dissected neoplastic and normal gastric epithelia. We identified 91,334 expressed tags, including 26,633 that were unique. The 20 most up-regulated genes (P < 0.01) in gastric cancer (GC) compared with normal gastric epithelia included several keratins that are specific for epithelial cells such as keratin 6A, 13, and 17. Interestingly, five calcium-binding proteins (S100A2, S100A7, S100A8, S100A9, and S100A10) were overexpressed. Quantitative real-time PCR on primary GC samples demonstrated overexpression of S100A2 in 18 of 20 tumors (90%). The other calcium-binding proteins were overexpressed in 25-45% of the GC samples that we studied. Our results indicate that S100A proteins may be important for gastric tumorigenesis. Additional investigations are required to elucidate the biological role of calcium-binding proteins in cancer.
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PMID:Gastric cancers overexpress S100A calcium-binding proteins. 1246 Aug 93

This article presents new information regarding the complement/level of S100 family members expressed in the brain and reviews the contribution of brain S100 family members to nervous system function and disease. A total of ten S100 family members are reported in the literature to be expressed in brain -S100A1, S100A2, S100A4, S100A5, S100A6, S100A10, S100A11, S100A13, S100B, and S100Z. Quantitative Northern blot analysis detected no S100A3, S100A8, S100A9 or S100A14 mRNA in mouse brain suggesting that these family members are not expressed in the brain. In addition, there was a 100-fold range in the mRNA levels for the six family members that were detected in mouse brain: S100A1/S100B levels were 5-fold higher than S100A6/S100A10 levels and 100-fold higher than S100A4/S100A13 levels. Five of these six family members (S1100A1, S100A6, S100A10, S100A13, and S100B) exhibited age-dependent increases in expression in adult mice that ranged from 5- to 20-fold. Although previous studies on S100 function in the nervous system have focused on S100B, other family members (S100A1, S100A3, S100A4, S100A5) have been implicated in neurological diseases. Like S100B, intra- and inter-cellular forms of these family members have been linked to cell growth, cell differentiation, and apoptotic pathways. Studies presented here demonstrate that ablation of S100A1 expression in PC12 cells results in increased resistance to Abeta peptide induced cell death, stabilization of intracellular [Ca2+] homeostasis, and reduced amyloid precursor protein expression. Altogether, these results confirm that S100-mediated signal transduction pathways play an important role in nervous system function/disease and implicate S100A1 in the neuronal cell dysfunction/death that occurs in Alzheimer's disease.
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PMID:S100-mediated signal transduction in the nervous system and neurological diseases. 1617 56

Evidence is accumulating to suggest that some of the diverse functions associated with BRCA1 may relate to its ability to transcriptionally regulate key downstream target genes. Here, we identify S100A7 (psoriasin), S100A8, and S100A9, members of the S100A family of calcium-binding proteins, as novel BRCA1-repressed targets. We show that functional BRCA1 is required for repression of these family members and that a BRCA1 disease-associated mutation abrogates BRCA1-mediated repression of psoriasin. Furthermore, we show that BRCA1 and c-Myc form a complex on the psoriasin promoter and that BRCA1-mediated repression of psoriasin is dependent on functional c-Myc. Finally, we show that psoriasin expression is induced by the topoisomerase IIalpha poison, etoposide, in the absence of functional BRCA1 and increased psoriasin expression enhances cellular sensitivity to this chemotherapeutic agent. Therefore, we identified a novel transcriptional mechanism that is likely to contribute to BRCA1-mediated resistance to etoposide.
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PMID:BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage-inducible gene. 1628 14

The S100 proteins act as multifactional signaling factors that are involved in the regulation of diverse cellular processes. To explore the involvement of S100 genes in bladder cancers, S100 gene expressions were systematically evaluated at the RNA level by microarray and real-time PCR. Total RNAs were obtained from 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced mouse and rat bladder cancers, human bladder cancers and matched normal bladder urothelium. Microarray analysis was performed on mouse and rat bladder cancers; real-time PCR was performed in mouse, rat and human bladder cancers and their matched normal urothelium for confirmation. Microarray analysis revealed that 9 and 6 members of the S100 gene family were differentially expressed in mouse and rat bladder cancers, respectively. Thirteen members of the S100 gene family were confirmed by real-time PCR to be differentially expressed in human bladder cancers, with overexpression of S100A2, S100A3, S100A5, S100A7, S100A8, S100A9, S100A14, S100A15, S100A16 and S100P, and underexpression of S100A1, S100A4 and S100B. S100A1, S10OA3, S100A8, S10A9, S100A14, S100A15 and S100A16 showed similar patterns of differential expression in bladder cancers from mouse, rat and human. To our knowledge this is the first report of systematic evaluation of S100 gene expressions in bladder cancers. Our results indicate that differential expression of S100 gene family members is characteristic of bladder cancers and these genes may play important roles in bladder tumorigenesis and progression.
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PMID:Expression of S100 protein family members in the pathogenesis of bladder tumors. 1797 44

Calcium (Ca(2+)) signaling plays a major role in a wide range of physiological functions including control and regulation of cardiac and skeletal muscle performance and vascular tone. As all Ca(2+) signals require proteins to relay intracellular Ca(2+) oscillations downstream to different signaling networks, a specific toolkit of Ca(2+)-sensor proteins involving members of the EF-hand S100 Ca(2+) binding protein superfamily maintains the integrity of the Ca(2+) signaling in a variety of cardiac and vascular cells, transmitting the message with great precision and in a temporally and spatially coordinated manner. Indeed, the possibility that S100 proteins might contribute to heart and vascular diseases was first suggested by the discovery of distinctive patterns of S100 expression in healthy and diseased hearts and vasculature from humans and animal heart failure (HF) models. Based on more elaborate genetic studies in mice and strategies to manipulate S100 protein expression in human cardiac, skeletal muscle and vascular cells, it is now apparent that the integrity of distinct S100 protein isoforms in striated muscle and vascular cells such as S100A1, S100A4, S100A6, S100A8/A9 or S100B is a basic requirement for normal cardiovascular and muscular development and function; loss of integrity would naturally lead to profound deregulation of the implicated Ca(2+) signaling systems with detrimental consequences to cardiac, skeletal muscle, and vascular function. The brief debate and discussion here are confined by design to the biological actions and pathophysiological relevance of the EF-hand Ca(2+)-sensor protein S100A1 in the heart, vasculature and skeletal muscle with a particular focus on current translational therapeutic strategies. By virtue of its ability to modulate the activity of numerous key effector proteins that are essentially involved in the control of Ca(2+) and NO homeostasis in cardiac, skeletal muscle and vascular cells, S100A1 has been proven to play a critical role both in cardiac performance, blood pressure regulation and skeletal muscle function. Given that deregulated S100A1 expression in cardiomyocytes and endothelial cells has recently been linked to heart failure and hypertension, it is arguably a molecular target of considerable clinical interest as S100A1 targeted therapies have already been successfully investigated in preclinical translational studies.
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PMID:S100A1 in cardiovascular health and disease: closing the gap between basic science and clinical therapy. 1953 70


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