Résumé
It is commonly assumed that the p53 tumor suppressor pathway is deregulated in most if not all human cancers. Thus, the past two decades have witnessed intense efforts to identify and characterize the growth-suppressive properties of p53 as well as the proteins and mechanisms involved in regulating p53 activity. In retrospect, it may therefore not be surprising that p53 was one of the very first mammalian proteins that were identified as physiologically relevant substrate proteins of the ubiquitin-proteasome system. Since then, plenty of evidence has been accumulated that p53 is in part controlled by canonical (i.e., resulting in proteasome-mediated degradation) and noncanonical (i.e., nonproteolytic) ubiquitination and by modification with the ubiquitin family members SUMO-1 and NEDD8. In this chapter, we will largely neglect the plethora of mechanisms that have been reported to be involved in the regulation of p53 ubiquitination but will focus on the enzymes and components of the respective conjugation systems that have been implicated in p53 modification and how the respective modifications (ubiquitin, SUMO-1, NEDD8) may impinge on p53 activity.