Two cellular proteins that bind to wild-type but not mutant p53.
p53 is a tumor-suppressor protein that can activate and repress transcription. Using the yeast two-hybrid system, we identified two previously uncharacterized human proteins, designated 53BP1 and 53BP2, that bind to p53. 53BP1 shows no significant homology to proteins in available databases, whereas 53BP2 contains two adjacent ankyrin repeats and a Src homology 3 domain. In vitro binding analyses indicate that both of these proteins bind to the central domain of p53 (residues 80-320) required for site-specific DNA binding. Consistent with this finding, p53 cannot bind simultaneously to 53BP1 or 53BP2 and to a DNA fragment containing a consensus p53 binding site. Unlike other cellular proteins whose binding to p53 has been characterized, both 53BP1 and 53BP2 bind to the wild-type but not to two mutant p53 proteins identified in human tumors, suggesting that binding is dependent on p53 conformation. The characteristics of these interactions argue that 53BP1 and 53BP2 are involved in some aspect of p53-mediated tumor suppression.
Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794-5222.
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Iwabuchi
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Bartel
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Li
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Marraccino
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Fields
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000378:metabolism
D017487:Ankyrins; D002352:Carrier Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; D005982:Glutathione Transferase; D001616:beta-Galactosidase