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[Cancer Research 60, 3722-3726, July 15, 2000]
© 2000 American Association for Cancer Research


Advances in Brief

Identification of Fractalkine, a CX3C-type Chemokine, as a Direct Target of p531

Kenji Shiraishi, Seisuke Fukuda, Toshiki Mori, Koichi Matsuda, Tatsuya Yamaguchi, Chizu Tanikawa, Michio Ogawa, Yusuke Nakamura2 and Hirofumi Arakawa

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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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 2000 by the American Association for Cancer Research.