The tumor suppressor p53 is highly regulated under various states of cellular stress. p53 stability is predominantly regulated through the ubiquitin-proteasomal pathway by the E3 ligase Mdm2. p53 ubiquitination is a dynamic process with Mdm2 capable of catalyzing both mono- and polyubiquitination. Additionally, deubiquitination is an important step occurring in p53 and Mdm2 stabilities. Factors such as HAUSP, p14(ARF), and MdmX play important regulatory roles in p53 ubiquitination/deubiquitination and their interplay with Mdm2 and p53 compound layers of complexity for regulating this important pathway.
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