Buck Martina
Department of Medicine, Veterans Healthcare Medical Center, San Diego, CA 92161, USA.
Cancer Lett. 2008 Sep 8;268(1):137-45. doi: 10.1016/j.canlet.2008.03.061. Epub 2008 May 22.
The interactions between BRCA1 and p53 are relevant for understanding hereditary breast and ovarian cancer. Although in vitro studies reported that BRCA1 (amino acids 224-500) and the second BRCT domain of the BRCA1 C-terminus may interact with p53, quantitative biophysical measurements indicate that these regions of BRCA1 do not bind efficiently to p53. Here we show that BRCA1 interacts with p53 in vivo in breast cancer cells, through another BRCA1 domain (amino acids 772-1292). Expression of a truncated BRCA1 (amino acids 772-1292) stimulated p53 DNA-binding and transcription activities and apoptosis, recapitulating some effects of DNA damage. These results suggest that a novel domain of BRCA1 may interact with p53 in breast cancer cells.
BRCA1与p53之间的相互作用对于理解遗传性乳腺癌和卵巢癌具有重要意义。尽管体外研究报告称BRCA1（氨基酸224 - 500）和BRCA1 C末端的第二个BRCT结构域可能与p53相互作用，但定量生物物理测量表明BRCA1的这些区域不能有效地与p53结合。在此我们表明，在乳腺癌细胞中，BRCA1通过另一个BRCA1结构域（氨基酸772 - 1292）在体内与p53相互作用。截短的BRCA1（氨基酸772 - 1292）的表达刺激了p53的DNA结合和转录活性以及细胞凋亡，概括了DNA损伤的一些效应。这些结果表明，BRCA1的一个新结构域可能在乳腺癌细胞中与p53相互作用。
