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

p53结合蛋白53BP1和53BP2的生理功能及其在癌细胞中的变化

• 批准号: 08680750
• 负责人: IWABUCHI Kuniyoshi
• 金额: $ 1.54万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08680750/
• 关键词: Tumor Suppressor Gene; p53; 53BP1; 53BP2; Transcription Factor; BRCT Domain; p53結合蛋白質

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.

p53 是一种肿瘤抑制蛋白，通过调节生长控制基因的表达来控制细胞增殖。在之前的研究中，我们鉴定了两种蛋白 53BP1 和 53BP2，它们能够通过 p53 的 DNA 结合域与野生型结合，但不能与突变型 p53 结合。我们分离了表达全长人 53BP1 克隆的 cDNA，该克隆预测在 H358 人肺癌细胞系中检测到的 1972 个残基的蛋白质。 53BP1和53BP2基因分别定位于染色体15q15-21和1q41-42。免疫荧光研究显示 53BP1 的三种染色模式：细胞质和细胞核；均质核；和核点图案。相比之下，53BP2 只定位于细胞质，并且这种模式在野生型 p53 共表达时不会改变。尽管我们之前的研究表明p53不能同时与53BP1或53BP2以及携带共有结合位点的DNA结合，但53BP1和53BP2都增强了p53介导的转录激活，这表明这些蛋白质可能在信号转导途径中发挥作用，以促进p53 活性。