Ganguli Gitali, Wasylyk Bohdan
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch cedex, France.
Mol Cancer Res. 2003 Dec;1(14):1027-35.
The tumor suppressor p53 is inactivated by overexpression of MDM2 in about 10% of human tumors. However, p53 is inactivated by other mechanisms in the majority of tumors, raising the possibility that MDM2 may be irrelevant to transformation in most cases. However, MDM2 has been reported to have p53-independent functions, in cell cycle control, differentiation, cell fate determination, DNA repair, basal transcription, and other processes. Furthermore, MDM2 appears to contribute to the transformed phenotype in the absence of wild-type p53. Nevertheless, the number of studies is still limited, and the evidence in some cases does not unequivocally show that the functions are p53 independent. We will discuss the circuits of regulation involving MDM2 that do not directly concern p53. Hopefully, future work will consolidate our understanding of the p53-independent pathological functions of MDM2 and will lead to useful therapeutic interventions that target the majority of tumors.
肿瘤抑制因子p53在约10%的人类肿瘤中因MDM2的过表达而失活。然而，在大多数肿瘤中p53是通过其他机制失活的，这增加了在大多数情况下MDM2可能与肿瘤转化无关的可能性。然而，据报道MDM2在细胞周期调控、分化、细胞命运决定、DNA修复、基础转录及其他过程中具有不依赖p53的功能。此外，在缺乏野生型p53的情况下，MDM2似乎也有助于形成转化表型。然而，相关研究的数量仍然有限，而且在某些情况下的证据并不能明确表明这些功能是不依赖p53的。我们将讨论涉及MDM2的不直接与p53相关的调控回路。希望未来的研究能够巩固我们对MDM2不依赖p53的病理功能的理解，并能带来针对大多数肿瘤的有效治疗干预措施。
