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)

S100 proteins are differentially expressed in tumours of epithelial origin. Little is known about their expression in melanocyte-derived tumours of neuroectodermal origin. We have analysed the expression of some S100 proteins in this line of lesions using SAGE Genie informatics, cell culture and human tumour tissue. The pattern of expression of six S100 proteins was investigated at both the mRNA and protein levels, using quantitative real-time PCR, western blotting and immunohistochemical analysis. No differential expression was observed with respect to S100A4, S100A7, S100A8, S100A9 and S100A11. In contrast, S100A10 was downregulated in three melanoma cell lines compared with normal melanocytes. Using SAGE informatics, two-dimensional displays of microarray expression data from the NCI60_Novartis cell lines displayed a positive correlation between the expression of S100A10 and the expression of the proliferation marker, Ki67. Our data suggest that S100A10, like its binding partners S100A7 and annexin A2, is an oxidant-sensitive protein. In addition, higher expression of S100A10 was detected in melanocyte cell lines with long projections compared with melanoma cell lines with small ripples. In a panel of 47 melanocyte-derived lesions comprising melanocytic naevi and melanomas, S100A10 was expressed to varying degrees in the melanocytic lesions. The antigen was primarily expressed in regions with a strong proliferating or differentiating capacity, especially in regions in or near the epidermis. We suggest that S100A10 may play a role in the regulation of the proliferation or early maturation sequence of melanocytic lesions, and that it merits further study as a potential biomarker of activity.
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PMID:Expression patterns of S100 proteins in melanocytes and melanocytic lesions. 1952 Dec 63

S100B and S100A10 are dimeric, EF-hand proteins. S100B undergoes a calcium-dependent conformational change allowing it to interact with a short contiguous sequence from the actin-capping protein CapZ (TRTK12). S100A10 does not bind calcium but is able to recruit the N-terminus of annexin A2 important for membrane fusion events, and to form larger multiprotein complexes such as that with the cation channel proteins TRPV5/6. In this work, we have designed, expressed, purified, and characterized two S100-target peptide hybrid proteins comprised of S100A10 and S100B linked in tandem to annexin A2 (residues 1-15) and CapZ (TRTK12), respectively. Different protease cleavage sites (tobacco etch virus, PreScission) were incorporated into the linkers of the hybrid proteins. In situ proteolytic cleavage monitored by (1)H-(15)N HSQC spectra showed the linker did not perturb the structures of the S100A10-annexin A2 or S100B-TRTK12 complexes. Furthermore, the analysis of the chemical shift assignments ((1)H, (15)N, and (13)C) showed that residues T102-S108 of annexin A2 formed a well-defined alpha-helix in the S100A10 hybrid while the TRTK12 region was unstructured at the N-terminus with a single turn of alpha-helix from D108-K111 in the S100B hybrid protein. The two S100 hybrid proteins provide a simple yet extremely efficient method for obtaining high yields of intact S100 target peptides. Since cleavage of the S100 hybrid protein is not necessary for structural characterization, this approach may be useful as a scaffold for larger S100 complexes.
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PMID:Design of high-affinity S100-target hybrid proteins. 1982 97