Maréchal V
Service de Microbiologie, Hôpital Rothschild, Paris.
Pathol Biol (Paris). 1997 Dec;45(10):824-32.
The mdm2 cellular protooncogene is involved in many human tumors where it has been shown to be overexpressed, including sarcomas, osteosarcomas, gliomas and others. The Mdm2 protein is believed to be oncogenic by binding and inactivating the p53 and Rb tumor suppressor gene products and by activating the E2F-1/DP-1 transcription factors, thus promoting the G1 to S phase transition. The mdm2 gene is activated transcriptionally by p53, thus forming an autoregulatory negative feedback loop. This feedback loop is important in normal cells and when cells are exposed to various genotoxic agents. By activating its own negative regulator, p53 would signal the cells to resume proliferation after a p53-mediated G1 arrest in response to DNA damage. The review aims to detail the functions of Mdm2 in normal and tumor cells. We also discuss several recent data suggesting that Mdm2 may exhibit activities unrelated to its well known function as a negative regulator of p53 activities.
mdm2细胞原癌基因参与了许多人类肿瘤，在这些肿瘤中它被证明是过度表达的，包括肉瘤、骨肉瘤、神经胶质瘤等。Mdm2蛋白被认为具有致癌性，它通过结合并使p53和Rb肿瘤抑制基因产物失活，以及激活E2F-1/DP-1转录因子，从而促进G1期向S期的转变。mdm2基因由p53转录激活，从而形成一个自动调节的负反馈环。这个反馈环在正常细胞以及细胞暴露于各种基因毒性剂时都很重要。通过激活自身的负调节因子，p53会在p53介导的G1期因DNA损伤而停滞之后，向细胞发出恢复增殖的信号。这篇综述旨在详细阐述Mdm2在正常细胞和肿瘤细胞中的功能。我们还讨论了一些最新数据，这些数据表明Mdm2可能表现出与其作为p53活性负调节因子的著名功能无关的活性。
