Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:012675 (S100)
 6,012 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ring chromosome 21 results in deletions of chromosome 21. We report on a cytogenetic and molecular analysis of a 4-generation family segregating a stable ring chromosome 21 in 4 relatives. To investigate the molecular structure of the ring chromosome, we have analyzed the DNAs of the transmitted ring in a mother and her daughter. The daughter presented at the age of 2 years with severe growth retardation and microcephaly, whereas her mother had microcephaly but normal intelligence. High resolution chromosome analysis of both cases showed the ring chromosome to be r(21)(p13q22) resulting in deletions of 21p and 21q22. The molecular content of the ring chromosome was determined using quantitative Southern blot analyses of 5 random DNA sequences and 4 expressed genes assigned to chromosome 21 and mapping in the region of q22.3. We have shown that collagen type VI, alpha 2 (COL6A2,) S100 protein, beta polypeptide (neural), (S100B), and D21S44 are present in only one copy in both ring carriers, while CRYA1, CBS, D21S43, D21S42, D21S41, and D21S39 are present in two copies. These data and the breakpoints defining the deletion in these patients show that deletion of COL6A2 and S100B is compatible with normal function and confirm the physical map of 21q22.3 by placing COL6A2, S100B, and D21S44 in very distal 21q22.3. Patients with such small deletions provide unique models for understanding the biological and clinical significance of aneuploidy for specific expressed genes.
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PMID:Stable ring chromosome 21: molecular and clinical definition of the lesion. 130 61

The beta-subunit of S100 protein (S100 beta) is highly conserved in the mammalian brain. The gene coding for human S100 beta has been mapped to chromosome 21. In order to study the consequences of overexpression of the S100 beta gene, transgenic mice were generated by microinjection of a 17.3 kilobase human genomic fragment containing the three exons and the transcription control elements of the human S100 beta gene. Mice from four transgenic lines carried approximately 10-100 transgene copies. Northern blotting demonstrated a tissue-specific and gene dose-dependent expression of human S100 beta mRNA in mouse brain. Increased expression of S100 beta mRNA was correlated with an increased production of S100 beta protein. Examination of brain sections by in situ hybridization and immunocytochemistry indicated that S100 beta was localized globally to astrocytes, as well as to discrete neurons in the mesencephalic and motor trigeminal, facial, and lemniscus nuclei in both normal and transgenic mice. In peripheral tissues, human S100 beta was expressed at 10-50-fold lower levels than in brain. The strict gene dosage dependence and cell specificity of transgene expression suggest the presence of a locus control region (LCR) in the human S100 beta gene. The mice tolerated 10-100-fold higher than normal levels of S100 beta gene expression in brain without any gross physical or behavioral abnormalities. The high-level expression and cell specificity of the S100 beta promoter/LCR suggest that it may provide a valuable tool to direct the expression of other transgenic products to specific cell types in the CNS.
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PMID:Cell-specific expression of high levels of human S100 beta in transgenic mouse brain is dependent on gene dosage. 143 98

A novel member of the S100 protein family, present in human placenta, has been characterized by protein sequencing, cDNA cloning, and analysis of Ca(2+)-binding properties. Since the placenta protein of 95 amino acid residues shares about 50% sequence identity with the brain S100 proteins alpha and beta, we proposed the name S100P. The cDNA was expressed in Escherichia coli and recombinant S100P was purified in high yield. S100P is a homodimer and has two functional EF hands/polypeptide chain. The low-affinity site (Kd = 800 microM), which, in analogy to S100 beta, seems to involve the N-terminal EF hand, can be followed by the Ca(2+)-dependent decrease in tyrosine fluorescence. The high-affinity site, provided by the C-terminal EF hand, influences the reactivity of the sole cysteine which is located in the C-terminal extension (Cys85). Binding to the high-affinity site (Kd = 1.6 microM) can be monitored by fluorescence spectroscopy of S100P labelled at Cys85 with 6-proprionyl-2-dimethylaminonaphthalene (Prodan). The Prodan fluorescence shows a Ca(2+)-dependent red shift of the maximum emission wavelength from 485 nm to 502 nm, which is accompanied by an approximately twofold loss in integrated fluorescence intensity. This indicates that Cys85 becomes more exposed to the solvent in Ca(2+)-bound S100P, making this region of the molecule, the so-called C-terminal extension, an ideal candidate for a putative Ca(2+)-dependent interaction with a cellular target. In p11, a different member of the S100 family, the C-terminal extension which contains a corresponding cysteine (Cys82 in p11), is involved in a Ca(2+)-independent complex formation with the protein ligand annexin II. The combined results support the hypothesis that S100 proteins interact in general with their targets after a Ca(2+)-dependent conformational change which involves hydrophobic residues of the C-terminal extension.
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PMID:S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. 163 9

We used polyclonal antisera recognizing S100, a small acidic protein highly enriched in nervous tissue, to stain sections of embryonic chicken lumbosacral spinal cord and hindlimb. S100 immunoreactivity was detected in developing sensory neurons of the dorsal root ganglia (DRG) and motor neurons of the ventral spinal cord as early as embryonic day (E) 5, and staining persisted through hatching. In contrast, expression of S100 first became apparent in Schwann cells at E13, just before myelination, and was not detected in developing skin or muscle. Since S100 beta was present in motor and sensory neurons and is known to promote neuronal survival and neurite extension in vitro (Winningham-Major, Staecker, Barger, Coats, and Van Eldik, 1989), we tested the ability of S100 to promote neuron survival in an in ovo survival assay. Addition of S100 to chick embryos in ovo during the period of naturally occurring motor neuron cell death resulted in a significant increase in motor neuron survival, but had no effect on the in vivo survival of sensory neurons in the DRG. The findings that S100 is present in spinal motor neurons and that the addition of S100 enhances the survival of these cells in vivo are consistent with the possibility that S100 may act as a naturally occurring neuron survival factor during development.
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PMID:S100 is present in developing chicken neurons and Schwann cells and promotes motor neuron survival in vivo. 163 90

S100 protein is a calcium-binding protein composed of two subunits S100 alpha and S100 beta, which are expressed selectively by specific cell types. The distribution of S100 beta was examined among various tissues obtained at autopsy from 18 subjects with chronic lung disease and 10 control subjects. The presence of S100 beta in individual cell types was demonstrated by immunoperoxidase staining using polyclonal and monoclonal antibodies specific for S100 beta. In the 10 control subjects, positive staining was seen in a number of cell types that normally produce S100 alpha and S100 beta, (e.g., glial cells, melanocytes, chondrocytes) or only S100 beta, (e.g., Schwann cells). There was no staining of myocardial cells, skeletal muscle fibers, or kidney tubules, which normally produce S100 alpha but not S100 beta. In contrast, in the 18 subjects with chronic lung disease, all of the above cell types stained positively for S100 beta, showing that in these subjects cell types that ordinarily expressed only S100 alpha also expressed S100 beta. We suggest that the observed induction of S100 beta in these cell types seen in subjects with chronic lung disease was mediated by an elevation of cAMP levels secondary to bronchodilator therapy with beta-adrenergic agonists and phosphodiesterase inhibitors.
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PMID:Immunoreactivity of S100 beta in heart, skeletal muscle, and kidney in chronic lung disease: possible induction by cAMP. 166 55

To determine whether ocular melanomas are immunophenotypically identical to cutaneous melanomas, 34 primary and metastatic choroidal melanomas representing all major histotypes defined by the Callender's classification, plus one melanoma of the iris and one conjunctival melanoma, were subjected to a panel of immunostains designed to distinguish anaplastic biopsies of cutaneous melanomas from carcinomas and lymphomas. All ocular melanomas were found to express the intermediate filament vimentin but not keratin, and all but 2 were melanotic by immunostaining. Thirty-three of 34 (97%) choroidal melanomas were strongly stained with a rabbit polyclonal antibody (P-S100) developed against the S100 protein family. In contrast, none of 14 spindle cell type primary lesions was stained with a monoclonal antibody (MAB-079) specific for both S100 alpha and S100 beta, the best-characterized S100 polypeptides. Furthermore, only 2 of 5 epithelioid and 3 of 10 mixed-cell-type melanomas were weakly reactive. Overall, 14.7% (5 of 29) were stained. In comparison, MAB079 stained 85% of all cutaneous melanomas. Five metastases of choroidal melanomas (spindle B, epithelioid, and mixed cell types) from different organ sites also were stained by P-S100 but not by MAB079. These findings were corroborated by immunostaining with another monoclonal antibody (MAB4D4) specific for S100 beta. Differential staining by the polyclonal but not the monoclonal antibodies suggests the possible presence of a variant S100 polypeptide(s) in choroidal melanomas. Since S100 alpha, S100 beta, and related proteins appear to be physiologically important, additional studies of these S100 proteins may shed light on the etiology or pathology of choroidal melanomas.
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PMID:S100 immunophenotypes of uveal melanomas. 169 42

In order to clarify the reported discrepancies in S100 alpha protein and mRNA distribution in rat tissues, a rat S100 alpha cDNA has been isolated and this species homologous probe along with a rat S100 beta cDNA probe has been used to examine S100 mRNA expression in rat tissues. Although the rat S100 alpha cDNA was missing approximately 30 nucleotides of coding sequence, only 4 conservative changes in amino acid sequence were observed when the deduced amino acid sequence was compared to the bovine S100 alpha amino acid sequence. Thus, S100 alpha proteins, like S100 beta proteins, are highly conserved among species. All nineteen of the tissues examined (including cerebrum and cerebellum) contained S100 alpha mRNA. In addition, S100 beta mRNA was detected in thirteen of the nineteen tissues examined. These results are in agreement with previous protein distribution studies and further demonstrate that S100 proteins are not brain-specific and are expressed in a large number of tissues. Although S100 alpha and S100 beta mRNAs were detected in rat tissues which had previously been reported to contain S100 alpha and S100 beta protein, a direct correlation between the protein and mRNA levels were not observed, suggesting that different mechanisms regulate S100 expression in various tissues. S100 alpha exhibited a single similar size mRNA species (0.5 Kb) in all tissues examined, as did S100 beta (1.5 Kb), suggesting that the individual S100 proteins are expressed as single mRNA and protein products in rat tissues.
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PMID:Isolation of a rat S100 alpha cDNA and distribution of its mRNA in rat tissues. 174 2

In this study radioimmunoassay, immunohistochemistry, Northern blot analysis, and a gel overlay technique have been used to examine the level, subcellular distribution, and potential target proteins of the S100 family of calcium-modulated proteins in adult and developing rat skeletal muscles. Adult rat muscles contained high levels of S100 proteins but the particular form present was dependent on the muscle type: cardiac muscle contained exclusively S100 alpha, slow-twitch skeletal muscle fibers contained predominantly S100 alpha, vascular smooth muscle contained both S100 alpha and S100 beta, and fast-twitch skeletal muscle fibers contained low but detectable levels of S100 alpha and S100 beta. While the distribution of S100 mRNAs paralled the protein distribution in all muscles there was no direct correlation between the mRNA and protein levels in different muscle types, suggesting that S100 protein expression is differentially regulated in different muscle types. Immunohistochemical analysis of the cellular distribution of S100 proteins in adult skeletal muscles revealed that S100 alpha staining was associated with muscle cells, while S100 beta staining was associated with nonmuscle cells. Radioimmunoassays of developing rat skeletal muscles demonstrated that all developing muscles contained low levels of S100 alpha at postnatal day 1 and that as development proceeded the S100 alpha levels increased. In contrast to adult muscle S100 alpha expression was confined to fast-twitch fibers in developing skeletal muscle until postnatal day 21. At postnatal day 1, developing contractile elements were S100 alpha positive, but no staining periodicity was detectable. At postnatal day 21, S100 alpha exhibited the same subcellular localization as seen in the adult: colocalization with the A-band and/or longitudinal sarcoplasmic reticulum. Comparison of the S100 alpha-binding protein profiles in fast- and slow-twitch fibers of various species revealed few, if any, species- or fiber type-specific S100 binding proteins. Isolated sarcoplasmic reticulum fractions and myofibrils contained multiple S100 alpha-binding proteins. The colocalization of S100 alpha and S100 alpha-binding proteins with the contractile apparatus and sarcoplasmic reticulum suggest that S100 alpha may regulate excitation and/or contraction in slow-twitch fibers.
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PMID:Examination of the calcium-modulated protein S100 alpha and its target proteins in adult and developing skeletal muscle. 180 19

Specific anti-calmodulin rabbit polyclonal and murine monoclonal antibodies have been produced with a thyroglobulin-linked peptide corresponding to amino acids 128-148 of bovine brain calmodulin. The monoclonal antibody is IgG-1 with kappa light chains. Both sets of antibodies recognize native vertebrate calmodulin, with the polyclonal antibody exhibiting an approximately fourfold higher sensitivity than the monoclonal antibody in a radioimmunoassay. The affinity of both polyclonal and monoclonal antibodies is approximately 2.5-fold higher for Ca(2+)-free calmodulin than for Ca(2+)-calmodulin. Other selected members of the calmodulin family (S100, troponin, and parvalbumin) do not exhibit significant cross-reactivity with the monoclonal antibody. Troponin and S100 beta displace some 125I-calmodulin from the polyclonal antibody, but require at least 900-fold excess concentration. The monoclonal antibody recognizes intact vertebrate calmodulin in solution and also on solid-phase. In addition, plant calmodulin and some forms of post-translationally modified calmodulin (phosphorylated or glycated) bind the monoclonal antibody. The affinity of the monoclonal antibody is approximately 5 x 10(8) liters/mol determined by displacement of 125I-calmodulin. On dot blotting the sensitivity for vertebrate calmodulin is 50 pg. The epitope for the monoclonal antibody is in the carboxyl terminal region (residues 107-148) of calmodulin. This highly specific anti-calmodulin monoclonal antibody should be a useful reagent in elucidating the mechanism by which calmodulin regulates intracellular metabolism.
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PMID:Monoclonal antibody to calmodulin: development, characterization, and comparison with polyclonal anti-calmodulin antibodies. 186 39

The changes in the levels of S100 beta (a protein that stimulates neurite extension and neuronal survival) and 42A and 42C (S100-like proteins whose mRNAs are induced in PC12 cells by nerve growth factor) during development and after rat sciatic nerve lesions were analyzed. S100 beta, 42A, and 42C mRNAs showed differential regulation during development. S100 beta mRNA was present both in sciatic nerve and brain, and increased more than 11-fold during the first 3 wk of nerve postnatal development. 42A and 42C mRNAs were essentially restricted to sciatic nerve, with little found in either embryonic or adult brain. The levels of 42C and 42A mRNAs in sciatic nerve increased 4- and 14-fold, respectively, by postnatal day 23 compared to postnatal day 2. 42A, 42C, and S100 beta mRNAs also showed a differential regulation during sciatic nerve degeneration and regeneration. Axotomized and control sciatic nerves were examined by Northern blots at various times after a crush or cut injury. 42A and 42C mRNA levels increased rapidly in the distal segment of axotomized nerve, remained two- to five-fold higher than controls at day 14 after injury but returned to control levels by 40 days. In contrast, S100 beta mRNA showed a three-fold decrease in the axotomized nerve between days 1 and 3 after injury, and slowly returned towards control levels over the next few weeks. The decrease in S100 beta mRNA was reflected by a corresponding decrease in S100 beta protein levels. The induction of 42A and 42C mRNAs and repression of S100 beta mRNA remained if nerve regeneration was prevented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential regulation of S100 beta and mRNAs coding for S100-like proteins (42A and 42C) during development and after lesion of rat sciatic nerve. 189 Jun 96


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