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Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan [K. S., S. F., T. M., K. M., T. Y., C. T., Y. N., H. A.], and Department of Surgery II, Kumamoto University Medical School, Kumamoto 860-8556, Japan [K. S., M. O.]
Fractalkine is a CX3C-type chemokine that induces chemotaxis of monocytes and cytotoxic T cells. Using the differential display method for examining gene expression in p53-defective cells transfected by adenovirus containing wild-type p53, we observed that fractalkine was induced by ectopic expression of p53. An electrophoretic mobility shift assay showed that a potential p53-binding site present in the promoter of the fractalkine gene could bind to p53 protein. Moreover, a heterogeneous reporter assay indicated that this promoter sequence possessed p53-dependent transcriptional activity. The strong induction of fractalkine when p53 protein was expressed by a wild-type transgene in p53-defective cells brought to light a novel role for p53; that is, potential elimination of damaged cells by the host immune response system through transcriptional regulation of fractalkine. Our results imply a pivotal role of p53 in immunosurveillance to prevent cells from undergoing malignant transformation.
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