Genome pharmacology on novel calcium signaling in diseases

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Recently, we purified S100C, a novel CィイD12+ィエD1-binding protein and cloned and sequenced its cDNA. S100C is a novel member of S100 protein family, exhibiting several unique properties. S100 proteins became of major interest because of their close association with several human diseases and their use as prognostic indicators of different tumor types. S100C was found to be highly expressed in colorectal center, suggesting a role in cell transformation, in agreement with the localization of the S100C gene on human chromosome 1q21 a region most frequently amplified in tumor tissues. The purpose of this study was to investigate the differential expression of S100C in a number of human tissues and to determine the distinct intracellular localization of S100C by confocal laser scanning microscopy to obtain more information about S100 protein cell signaling. Moreover, we found that S100C interacts not only with annexins as previous reported, but also with actin in a CィイD12+ィエD1-dependent manner. In conclusion, (1) A single species of transcript of expected size (about 0.5 kb) was detected at high level in placenta. Intermediate levels were found in adult heart, adult and fatal lung and kidney, as well as adult pancreas. Low levels were detected in adult skeletalmuscle, as well as adult and fetal liver, S100C was barely detectable in fetal or adult brain. However, S100C is predominantly localized in the nucleus and less in the cytoplasm of tumor cells. (2) we found that S100C is abundant in smooth muscle and is a CィイD12+ィエD1-dependent actin binding protein. Further, S100C inhibits actin-activated myosin MィイD12+ィエD1-ATPase activity by binding to actin only in the presence on CaィイD12+ィエD1. Our results suggest that S100C is a CィイD12+ィエD1DA-dependent actin binding protein and is involved in the CィイD12+ィエD1DA-dependent regulation of action filaments.