I n agreement with the notion that selective protein degradation is involved in the regulation of m any cell regu latory processes, there is increasing evidence that deregulation of degradation can contribute to carcinogenesis. Many proto-oncogene pro ducts, for example c-jun , 1 are very short-lived and increases in their intracellu lar con centration can contribute to cellular trans formation indicating that the turnover rate of such proteins must be tightly controlled (for example see refs. 2-4). Indeed, in contrast to c-jun, the retroviral oncogene product v-jun is not targeted for degradation by the ubiquitin/proteasome system. 5 This results in increased levels of v-jun and, therefore, explains at least in part its transforming potential. 2’6 Another prominent example for the significance of selective turnover in cellular transformation is provided by the tumor suppressor protein p5 3 which plays a key role in human carcinogenesis. Activation of the growth suppressive properties of p 5 3 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 p5 3 activation. In the following, the potential role of the ubiquitin/proteasome system in p5 3 degra dation and possible mechanisms involved in p 5 3 stability regulation will be discussed.