Phsiologic function and its change in cancer cells of p53-binding proteins, 53BP1 and 53BP2

p53是一种肿瘤抑制蛋白，其通过调节生长控制基因的表达来控制细胞增殖。在先前的研究中，我们鉴定了两种蛋白质，53 BP 1和53 BP 2，它们能够通过p53的DNA结合结构域与野生型p53结合，但不能与突变型p53结合。我们分离表达全长人53 BP 1克隆的cDNA，其预测在H358人肺癌细胞系中检测到的1972个残基的蛋白。53 BP 1和53 BP 2基因分别定位于染色体15 q15 -21和1 q41 -42。免疫荧光研究显示三种类型的53 BP 1染色模式：细胞质和细胞核;均匀的核;和核斑点图案。相反，53 BP 2只定位于细胞质，并且这种模式在野生型p53共表达后没有改变。虽然我们以前的研究表明，p53不能同时结合到任何53 BP 1或53 BP 2和DNA携带的共识结合位点，53 BP 1和53 BP 2增强p53介导的转录激活，这表明这些蛋白可能在信号转导途径中发挥作用，以促进p53的活性。

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 to wild type but not to mutant p53 via the DNA-binding domain of p53. We isolated cDNAs expressing a full-length human 53BP1 clone, which predicts a protein of 1972 residues which is detected in the H358 human lung carcinoma cell line. The 53BP1 and 53BP2 genes were mapped to chromosomes 15q15-21 and 1q41-42, respectively. Immunofluorescence studies showed three types of staining pattern for 53BP1 : both cytoplasmic and nuclear ; homogeneous nuclear ; and nuclear dot patterns. In contrast, 53BP2 localized exclusively to the cytoplasm, and this pattern did not change upon coexpression of wild type p53. Although our previous study revealed that p53 is not able to bind simultaneously to either 53BP1 or 53BP2 and to DNA carrying a consensus binding site, both 53BP1 and 53BP2 enhanced p53-mediated transcriptional activation, suggesting that these proteins might function in signal transduction pathways to promote p53 activity.