Milner J, Watson J V
Department of Pathology, Cambridge University, UK.
Oncogene. 1990 Nov;5(11):1683-90.
Using analytical flow cytometry we have monitored changes in the conformation of p53 through the cell cycle under different conditions of cell growth. Conformational variants of murine p53 are characterized by reactivity with monoclonal antibodies PAb246, PAb248 and PAb421. In proliferating cells, p53 conformation was independent of the cell cycle. Addition of fresh medium, however, resulted in loss of p53 reactivity with PAb246 (p53-246(0]. Mutant p53, which lacks suppressor function, is also p53-246(0). Thus in SV3T3 cells p53-246(0) may reflect a change in p53 tertiary structure that is induced by growth stimulation and is compatible with the normal cell growth response. We argue that p53-246(0) and p53-246+ may exert positive and negative constraints in cell growth control. By stabilising p53-246(0) activating mutants of p53 would favour cell proliferation with dominant effect.
利用分析流式细胞术，我们监测了在不同细胞生长条件下，p53构象在细胞周期中的变化。小鼠p53的构象变体通过与单克隆抗体PAb246、PAb248和PAb421的反应性来表征。在增殖细胞中，p53构象与细胞周期无关。然而，添加新鲜培养基会导致p53与PAb246的反应性丧失（p53-246(0)）。缺乏抑制功能的突变型p53也是p53-246(0)。因此，在SV3T3细胞中，p53-246(0)可能反映了由生长刺激诱导的p53三级结构变化，并且与正常细胞生长反应一致。我们认为p53-246(0)和p53-246+可能在细胞生长控制中发挥正向和负向限制作用。通过稳定p53-246(0)，p53的激活突变体将以显性效应促进细胞增殖。
