Zhang W, Randhawa G S, Guo X Y, Deisseroth A B
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cell Growth Differ. 1994 Jul;5(7):705-10.
Normal p53 protein suppresses cell proliferation and ras oncogene-induced cell transformation. Missense mutations in the middle conserved conformational domain of p53 decrease its antiproliferation function. In this work, we studied the requirement of the NH2- and COOH-terminal regions of p53 in its antiproliferation function using two independent assays, growth of chronic myelogenous leukemia K562 cells on methylcellulose semisolid medium and ras oncogene-induced focus formation of rat fibroblast cells (Rat-1). We found that deletion of 80 or 159 amino acids from the NH2-terminus and deletion of 67 amino acids from the COOH-terminus of p53 drastically reduced the antiproliferation function of p53. However, the COOH-terminal deletion mutant is capable of binding to a p53 DNA-binding element, p53CON (GGACATGCCCGGGCATGTCC), and of activating p53CON-mediated transcription. These results suggest that p53' abilities to bind p53CON and activate transcription are not sufficient for its antiproliferation function and that p53CON-regulated genes may not be growth suppressive.
正常的p53蛋白可抑制细胞增殖和ras癌基因诱导的细胞转化。p53中间保守构象域的错义突变会降低其抗增殖功能。在本研究中，我们使用两种独立的检测方法，即慢性髓性白血病K562细胞在甲基纤维素半固体培养基上的生长以及ras癌基因诱导的大鼠成纤维细胞（Rat-1）的集落形成，研究了p53的NH2端和COOH端区域在其抗增殖功能中的作用。我们发现，从p53的NH2端缺失80或159个氨基酸以及从COOH端缺失67个氨基酸会大幅降低p53的抗增殖功能。然而，COOH端缺失突变体能够与p53 DNA结合元件p53CON（GGACATGCCCGGGCATGTCC）结合，并激活p53CON介导的转录。这些结果表明，p53结合p53CON和激活转录的能力不足以实现其抗增殖功能，并且p53CON调控的基因可能不具有生长抑制作用。
