Asschert J G, Vellenga E, De Jong S, de Vries E G
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Anticancer Res. 1998 May-Jun;18(3A):1713-25.
The function of p53 tumour suppressor protein is determined by various intrinsic properties of the protein. The effect of p53 DNA-binding, and protein-protein interactions are determined by the conformation of the protein. Thus, p53 fulfils its role in cell cycle control and the onset of apoptotic cell death, which is altered when the wild-type p53 (wt-p53) conformation is changed due to mutation. This review focuses on the communal interactions of wt- and mutant p53 (m-p53) with growth factors and shows that m-p53 affects different cell biological functions that determine the malignant behaviour of cells. P53, for instance, affects the response of cells to growth factors and growth factor-withdrawal. Furthermore, p53 is involved in the expression of several growth factor- and growth factor receptor genes. These data suggest that restoration of the wt-p53 phenotype in tumour cells with m-53 might not only affect cell cycle control and apoptotic mechanisms but could also reduce autocrine growth and restore sensitivity to physiological growth inhibitors.
p53肿瘤抑制蛋白的功能由该蛋白的各种内在特性决定。p53与DNA结合的作用以及蛋白质与蛋白质之间的相互作用由该蛋白的构象决定。因此,p53在细胞周期控制和凋亡性细胞死亡的起始过程中发挥作用,当野生型p53(wt-p53)的构象因突变而改变时,其功能也会发生改变。本综述着重探讨了wt-p53和突变型p53(m-p53)与生长因子之间的共同相互作用,并表明m-p53会影响决定细胞恶性行为的不同细胞生物学功能。例如,p53会影响细胞对生长因子的反应以及生长因子的撤除。此外,p53还参与了多个生长因子和生长因子受体基因的表达。这些数据表明,在具有m-p53的肿瘤细胞中恢复wt-p53表型,可能不仅会影响细胞周期控制和凋亡机制,还可能会减少自分泌生长,并恢复对生理性生长抑制剂的敏感性。