Figure 3.

The pocket protein regulatory network is disrupted by multiple mechanisms in cancer. Tumor suppressors in the network are inactivated via point mutations or deletions (X) or via epigenetic silencing or increased proteolytic degradation (↓). Mutations and or deletions affecting pRB, p130, and p16 have been described (reviewed in Malumbres & Barbacid⁹⁴). Amplification of cyclins or defects in their degradation pathways is also common (↑). The pathway can be disrupted by a mutation on CDK4 that makes it resistant to CDK inhibitors (X). Deletions affecting expression of B55α have been described in a variety of cancers (see text) and may affect this equilibrium.