Interaction of major genes predisposing to hepatocellular carcinoma with genes encoding signal transduction pathways influences tumor phenotype and prognosis

Figure 1 Cell cycle protection from inhibition by P16^INK4A through the CDC37-HSP90 complex and CRM1 transporter protein. P16^INK4A forms complexes with CDK4 and CDK6 which, as a consequence, cannot by activated by Cyclin D1 and cannot phosphorylate pRb. The chaperons CDC37 and HSP90 form complexes with CDKs protecting them from inactivation by P16^INK4A. CRM1 forms a complex with E2F4, a P16^INK4A effector, transporting it outside of the nucleus, thus inactivating P16^INK4A.