Grossman S R, Perez M, Kung A L, Joseph M, Mansur C, Xiao Z X, Kumar S, Howley P M, Livingston D M
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Cell. 1998 Oct;2(4):405-15. doi: 10.1016/s1097-2765(00)80140-9.
Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.
p53 周转的调控对 p53 功能至关重要。E1A 与 p300/CBP 的结合会转化为 p53 稳定性的增强，这意味着这些共激活蛋白通常在 p53 周转调控中发挥作用。在这方面，p300 C/H1 区域作为 p53 和 MDM2（一种天然存在的 p53 去稳定剂）在体内的特异性结合位点。此外，大多数内源性 MDM2 与 p300 结合，并且遗传分析表明 p53 和 MDM2 与 p300 C/H1 的特异性相互作用是 MDM2 介导的 p53 周转的重要步骤。过量产生 p300 C/H1 结构域对 p53 的稳定作用突出了 p300 在内源性 p53 降解中的特定作用。综上所述，数据表明 p300/CBP C/H1、p53 和 MDM2 之间的特异性相互作用密切参与了 MDM2 介导的 p53 丰度调控。
