Figure 4.

Inactivation of pRb in HCC is complex. Deletion, mutation, or truncation of the pRb gene leads to an inactive form or complete absence of the pRb protein. Overexpression of the E6AP ubiquitin ligase or p28^Gankyrin in HCC enhances degradation of pRb while hyperactivity of Cdk/cyclin complexes inactivates pRb by sustained hyperphosphorylation. Those mechanisms impair pRb tumor suppressor activity and induce persistent E2F activity, triggering cell cycle progression as well as aneuploidy and chromosome instability.