KEEPING AN OLD FRIEND UNDER CONTROL - REGULATION OF P53 STABILITY

The tumor suppressor protein p53 plays a pivotal role in protection ag ainst the development of cancer and is inactivated in many human malig nancies. p53 is thought to prevent accumulation of genomic alterations by hindering cell proliferation in response to genotoxic stress, and two of the principal functions of p53 are the induction of cell-cycle arrest and the activation of apoptotic cell death. Because p53 is an e xtremely efficient inhibitor of cell growth, keeping p53 function unde r control in normal cells is critical. One of the principal mechanisms by which cells achieve this is by regulating the p53 protein level, a lthough the ability of the protein to adopt active and latent forms an d its cellular localization also contribute to the regulation of its f unction. Here, we summarize recently identified mechanisms that regula te the stability of the p53 protein and discuss the potentially immens e clinical relevance of these observations in developing therapeutical approaches that aim to restore p53 function in human tumors.