RNAi knockdown of HdmX or Hdm2 leads to new insights into p53 signaling.

摘要

The p53 tumor suppressor protein is a central player in the cellular response to stress and considerable evidence supports that p53 inactivation plays a critical in human tumorigenesis. While nearly half of all human tumors inactivate p53 through gene mutation or deletion, remaining tumors harbor inactive wild-type p53 protein through deregulation of various components in the p53 signaling pathway. A growing interest has developed in understanding the therapeutic implications of p53 reactivation by targeting p53 inhibitors. On the forefront of potential therapeutic targets are the p53 negative regulators Hdm2 and HdmX. Originally discovered as associating with p53, Hdm2 overexpression is seen in about 20% of human tumors, the majority harboring wild-type p53. HdmX over-expression is seen in a similar percentage of human tumors with retinoblastomas showing the highest percentage (65%) of HdmX deregulation.