Wang Y, Reed M, Wang P, Stenger J E, Mayr G, Anderson M E, Schwedes J F, Tegtmeyer P
Department of Microbiology, State University of New York, Stony Brook 11794.
Genes Dev. 1993 Dec;7(12B):2575-86. doi: 10.1101/gad.7.12b.2575.
We have investigated the DNA-binding, oligomerization, and trans-activation functions of isolated segments of murine p53. We find that p53 has two autonomous DNA-binding regions. One domain, from amino acid 280 to 390, forms stable tetramers and binds DNA nonspecifically. The biological significance, if any, of this DNA-binding activity is not known. A second domain, from amino acid 80 to 290, does not form stable tetramers under stringent conditions but binds DNA both specifically and nonspecifically. The specific DNA-binding function of p53, therefore, resides in the highly conserved central region of the protein and does not require stable tetramerization. Amino acids 1-290, which include both the specific DNA-binding domain and the amino-terminal acidic region, activate a p53-specific promoter in vivo. This finding strongly argues that the DNA-binding activity of p53 segment 80-290 is physiologically significant. The role of tetramerization in p53 function remains to be determined.
我们研究了小鼠p53分离片段的DNA结合、寡聚化及反式激活功能。我们发现p53有两个自主的DNA结合区域。一个结构域，从氨基酸280至390，形成稳定的四聚体并非特异性地结合DNA。这种DNA结合活性的生物学意义（如果有的话）尚不清楚。第二个结构域，从氨基酸80至290，在严格条件下不形成稳定的四聚体，但能特异性和非特异性地结合DNA。因此，p53的特异性DNA结合功能位于蛋白质高度保守的中心区域，且不需要稳定的四聚化。包括特异性DNA结合结构域和氨基末端酸性区域的氨基酸1 - 290在体内激活p53特异性启动子。这一发现有力地表明p53片段80 - 290的DNA结合活性具有生理意义。四聚化在p53功能中的作用仍有待确定。
