Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratocan, along with lumican and mimecan, represent the keratan sulfate-containing proteoglycans of the vertebrate cornea that play a key role in development and maintenance of corneal transparency. In this study, we cloned 4.1 kb of the human Kera 5'-flanking region and characterized the promoter structure. Using primer extension and ribonuclease protection assay, we identify two major transcriptional start sites in the first exon. Using luciferase reporter gene transfection analysis of 5'-deletion and mutation constructs, we demonstrate positive and negative regulatory elements within a 1.3 kb upstream sequence. Comparison of human and bovine 5'-flanking sequences reveals three highly conserved regions: a 450 bp region in the first exon, a 92 bp promoter proximal conserved regulatory region identified as an enhancer in the natural context, and a 223 bp promoter distal conserved regulatory region identified as a silencer both in the natural context and in a heterologous promoter system. In addition, a conserved CArG-box residing 851 bp upstream of the first transcription start site also can lead to the repression of Kera expression in cultured corneal keratocytes. DNaseI footprinting and electrophoretic mobility shift assay demonstrate that cell type-specific factors bind to regulatory elements located in the conserved regions. Competition experiments indicate that the CTC factor and a protein that binds to the CAGA motif are likely to be among the multiple factors involved in the transcriptional regulation of the human Kera gene.
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PMID:Identification and characterization of conserved cis-regulatory elements in the human keratocan gene promoter. 1089 81

Early detection is the key to improve the prognosis of kidney cancer. This study profiled and identified differentially expressed serum proteins in stage T1a renal cell carcinoma (RCC) using isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. A total amount of 99 serum samples including 29 patients with ccRCC, 24 patients with a benign kidney mass, 28 patients with another type of urological tumor (20 cases of transitional cell carcinoma and 8 cases of prostate cancer or a male genital tumor), and 18 healthy controls were subjected to iTRAQ-based mass spectrometry. ProteinPilot software was used to identify the differentially expressed serum proteins in RCC compared to the other three populations. Hierarchical clustering analysis according to The Cancer Genome Atlas (TCGA) RCC database was then performed as the cross-platform validation. Immunohistochemistry was performed to verify the expression of selected proteins in tissue samples from these subjects. iTRAQ identified 27 differentially expressed serum proteins in the RCC patients, and 11 of these proteins were cross validated in RCC tissues from the TCGA database. The expression of C1QC, C1QB, S100A8, S100A9, ceruplasmin, and lumican was verified and associated with the tumor stage and/or grade. There were 27 differentially expressed proteins in early-stage RCC identified by iTRAQ; among them, the expression of C1QC, C1QB, S100A8, S100A9, ceruplasmin, and lumican were associated with the tumor stage and/or grade. Further studies are needed to confirm these data for their use as biomarkers for the early detection of RCC.
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PMID:iTRAQ-based quantitative proteomic analysis reveals potential early diagnostic markers of clear-cell Renal cell carcinoma. 2731 73