Figure 5. Hypothetical role played by the ubiquitin code in proteasomal or autophagic degradation (see also text for explanation). While substrates modified by K48-linked ubiquitin chains are recognized by the proteasome, K63 chain formation is involved in a variety of other functions, including in the autophagic clearance of micro- or macro-aggregates. CHIP can catalyze K63 ubiquitination when in combination with Ubc13. In the case of MDM2 K63 chain formation required MDMX.³⁷ We speculate that K63-linked ubiquitin chains may play a role in autophagic disruption of mutant p53. Other studies have shown that mutant p53 localize in aggresomes, wherein misfolded proteins are either stored or cleared by autophagy.³¹ The observation that p300 inhibits autophagy⁴⁴ and is necessary for aggresome formation⁴³ raises the possibility that autophagic degradation of mutant p53 within aggresomes is regulated by the interaction with p300.