Ubiquitin, E6-AP, and their role in p53 inactivation.

Inactivation of the tumor suppressor protein p53 plays a key role in human carcinogenesis. Activation of the growth-suppressive properties of p53 by appropriate stress signals, including genotoxic stress, is generally accompanied by intracellular accumulation of the protein. This suggests that stabilization of the otherwise short-lived protein is an intrinsic feature of p53 activation. The ubiquitin/proteasome system is believed to be a major proteolytic system involved in selective degradation of cell regulatory proteins. In this review, the potential role of the ubiquitin/proteasome system in p53 degradation and possible mechanisms involved in p53 stability regulation are discussed.