von der Weth A, Deppert W
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.
J Virol. 1993 Feb;67(2):886-93. doi: 10.1128/JVI.67.2.886-893.1993.
To analyze the proposed growth-inhibitory function of wild-type p53, we compared simian virus 40 (SV40) DNA replication in primary rhesus monkey kidney (PRK) cells, which express wild-type p53, and in the established rhesus monkey kidney cell line LLC-MK2, which expresses a mutated p53 that does not complex with large T antigen. SV40 DNA replication proceeded identically in both cell types during the course of infection. Endogenously expressed wild-type p53 thus does not negatively modulate SV40 DNA replication in vivo. We suggest that inhibition of SV40 DNA replication by wild-type p53 in in vitro replication assays is due to grossly elevated ratios of p53 to large T antigen, thus depleting the replication-competent free large T antigen in the assay mixtures by complex formation. In contrast, the ratio of p53 to large T antigen in in vivo replication is low, leaving the majority of large T antigen in a free, replication-competent state.
为了分析野生型p53所提出的生长抑制功能，我们比较了表达野生型p53的原代恒河猴肾（PRK）细胞和已建立的恒河猴肾细胞系LLC-MK2中猿猴病毒40（SV40）的DNA复制情况，LLC-MK2细胞表达一种不与大T抗原形成复合物的突变型p53。在感染过程中，两种细胞类型中SV40的DNA复制情况相同。因此，内源性表达的野生型p53在体内不会对SV40的DNA复制产生负向调节作用。我们认为，在体外复制试验中野生型p53对SV40 DNA复制的抑制作用是由于p53与大T抗原的比例大幅升高，从而通过复合物的形成耗尽了试验混合物中有复制能力的游离大T抗原。相比之下，体内复制中p53与大T抗原的比例较低，使得大多数大T抗原处于游离的、有复制能力的状态。
