Regulation of p53 stability by Mdm2

摘要: The tumour-suppressor p53 is a short-lived protein that maintained at low, often undetectable, levels in normal cells. Stabilization of the response to an activating signal, such as DNA damage, results rapid rise and subsequent inhibition cell growth. Tight regulation function critical for growth development, one mechanism by which controlled through interaction with Mdm2 protein. inhibits cell-cycle arrest apoptic functions we show here can also result large reduction enhanced proteasome-dependent degradation. Endogenous are sufficient regulate stability, overexpression reduce amount endogenous p53. Because mdm2 transcriptionally activated p53, this degradative pathway may contribute maintenance low concentrations Furthermore, mechanisms regulating Mdm2-induced degradation play role controlling extent duration response.