Artificial regulation of p53 function by modulating its assembly

作者：Inobe Tomonao^*; Nozaki Miyuki; Nukina Nobuyuki

来源：Biochemical and Biophysical Research Communications, 2015, 467(2): 322-327.

DOI：10.1016/j.bbrc.2015.09.162

• p53
• Rapamycin
• FRB
• FKBP
• Chemically induced oligomerization
• Protein engineering

The tumor suppressor p53, a 393-amino acid transcription factor with four domains, induces cell cycle arrest, senescence, and apoptosis in response to diverse stress. Tetramer formation is critical for the function of p53. The tetramerization domain permits the tetramerization of p53, where bundled four DNA-binding domains recognize the specific target DNA sequences and activate hundreds of genes, which lead to the various cell fates. Here we show that tumor suppressive functions of p53 can be regulated by manipulating tetramer formation of an engineered p53, in which tetramerization domain of p53 is replaced with an inducible tetramer forming protein. This result suggests that artificial regulation of p53 activity by the engineered p53 is a useful tool to investigate the tumor suppression mechanism of p53 and to combat cancer.

• 出版日期2015-11-13