STIMULATION OF P53-MEDIATED TRANSCRIPTIONAL ACTIVATION BY THE P53-BINDING PROTEINS, 53BP1 AND 53BP2

p53 is a tumor suppressor protein that controls cell proliferation by regulating the expression of growth control genes. In a previous study , we identified two proteins, 53BP1 and 53BP2, that are able to bind t o wild type but not to mutant p53 via the DNA-binding domain of p53. W e isolated cDNAs expressing a full-length human 53BP1 clone, which pre dicts a protein of 1972 residues that can be detected in the H358 huma n lung carcinoma cell line. The 53BP1 and 53BP2 genes were mapped to c hromosomes 15q15-21 and 1q41-42, respectively. Immunofluorescence stud ies showed three types of staining patterns for 53BP1 as follows: both cytoplasmic and nuclear, homogeneous nuclear, and a nuclear dot patte rn. In contrast, 53BP2 localized exclusively to the cytoplasm, and thi s pattern did not change upon coexpression of wild type p53. Although our previous study revealed that p53 is not able to bind simultaneousl y to either 53BP1 or 53BP2 and to DNA carrying a consensus binding sit e, both 53BP1 and 53BP2 enhanced p53-mediated transcriptional activati on and induced the expression of a p53-dependent protein, suggesting t hat these proteins might function in signal transduction pathways to p romote p53 activity.