Identification of fractalkine, a CX3C-type chemokine, as a direct target of p53.
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.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.
K
K
Shiraishi
S
S
Fukuda
T
T
Mori
K
K
Matsuda
T
T
Yamaguchi
C
C
Tanikawa
M
M
Ogawa
Y
Y
Nakamura
H
H
Arakawa
D000256:Adenoviridae / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000528:radiation effects; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; D008565:Membrane Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D008156:Luciferases