FIG. 8.

Model on the role of hHR23, in p53 degradation. hHR23 can interact with the 26S proteasome via its N-terminal Ubl domain and with polyubiquitylated p53 via its C-terminal Uba domain. At appropriate levels, a given hHR23 molecule can thus simultaneously interact with the 26S proteasome and a polyubiquitylated p53 molecule, thereby facilitating degradation of p53 (A). After overexpression of hHR23 (B), formation of a ternary complex between polyubiquitylated p53, hHR23, and 26S proteasomes is disturbed, since the respective interaction sites for hHR23 on polyubiquitylated p53 and the 26S proteasome are occupied by two different hHR23 molecules. In consequence, p53 protein levels accumulate.