The role of ubiquitination in the direct mitochondrial death program of p53

p53 ubiquitination at C-terminal lysines by MDM2 and other E3 ligases had been considered a straightforward negative regulation of p53 with only one function, that is marking the protein for proteasomal degradation. In this review, we will focus on the recently uncovered activating role of ubiquitination in the transcription-independent direct mitochondrial death program of p53.