Hupp T R, Lane D P
Department of Biochemistry, Dundee University, Scotland.
Cold Spring Harb Symp Quant Biol. 1994;59:195-206. doi: 10.1101/sqb.1994.059.01.024.
p53 is an allosterically regulated protein with a latent DNA-binding activity. Posttranslational modification of a carboxy-terminal regulatory site in vitro, by casein kinase II and protein kinase C, can activate the sequence-specific DNA-binding function of the wild-type protein. The latent form of p53 is produced in a variety of eukaryotic and prokaryotic cell lines, including E. coli, Sf9 insect cells, and C6 cells, indicating that the activation of p53 in vivo is rate-limiting. In addition, phosphorylation of p53 at the protein kinase C site and activation in vivo correlate with the loss of reactivity of active p53 protein to the carboxy-terminal antibody, PAb421. These results suggest that two highly conserved protein kinases modify polypeptide structure through a common biochemical mechanism and that different enzymatic pathways may channel information into the carboxy-terminal regulatory site of p53, allosterically activating its function as a tumor suppressor.
p53是一种具有潜在DNA结合活性的变构调节蛋白。酪蛋白激酶II和蛋白激酶C在体外对羧基末端调节位点进行翻译后修饰，可激活野生型蛋白的序列特异性DNA结合功能。p53的潜在形式在多种真核和原核细胞系中产生，包括大肠杆菌、Sf9昆虫细胞和C6细胞，这表明p53在体内的激活是限速的。此外，p53在蛋白激酶C位点的磷酸化以及在体内的激活与活性p53蛋白对羧基末端抗体PAb421的反应性丧失相关。这些结果表明，两种高度保守的蛋白激酶通过共同的生化机制修饰多肽结构，并且不同的酶促途径可能将信息传递到p53的羧基末端调节位点，变构激活其作为肿瘤抑制因子的功能。
