Lindström Mikael S, Deisenroth Chad, Zhang Yanping
Department of Radiation Oncology, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599, USA.
Cell Cycle. 2007 Feb 15;6(4):434-7. doi: 10.4161/cc.6.4.3861. Epub 2007 Feb 18.
A number of events imparting instability to ribosomal biogenesis can cause nucleolar stress and trigger activation of a p53 checkpoint. Following nucleolar stress, ribosomal proteins L5, L11 and L23 bind to MDM2, blocking MDM2-mediated p53 ubiquitination and degradation. The MDM2 C4 zinc finger domain has been shown to play an important role in this process. Mutations targeting the C4 zinc finger of MDM2 have been reported in human cancers, and now a potential rationale for the occurrence of these mutations in cancer has emerged. Here we further discuss these findings and propose the existence of a ribosomal protein-MDM2-p53 surveillance network responsible for monitoring the stability of the transition between cell growth and division.
一些使核糖体生物合成不稳定的事件可导致核仁应激并触发p53检查点的激活。核仁应激后，核糖体蛋白L5、L11和L23与MDM2结合，阻断MDM2介导的p53泛素化和降解。MDM2的C4锌指结构域已被证明在这一过程中起重要作用。在人类癌症中已报道了靶向MDM2 C4锌指的突变，现在癌症中这些突变发生的潜在原因已经出现。在此，我们进一步讨论这些发现，并提出存在一个核糖体蛋白-MDM2-p53监测网络，负责监测细胞生长和分裂之间转变的稳定性。
