Watch the GAP: Emerging Roles for IQ Motif-Containing GTPase-Activating Proteins IQGAPs in Hepatocellular Carcinoma

Figure 2

Schema summarizing the proposed hypothesis for IQGAP1 and IQGAP2 involvement in HCC development. In wild-type hepatocytes, IQGAP2 exists in two pools-bound to β-catenin and anchored at the submembrane region along with E-cadherin and IQGAP1, and as a part of the β-catenin destruction complex consisting of GSK3β kinase, Axin and Adenomatous polyposis coli (APC). The β-catenin destruction complex prevents β-catenin activation and translocation to the nucleus. In Iqgap2 ^−/− hepatocytes, E-cadherin disappears from the membrane, while β-catenin escapes the destruction complex, accumulates in the cytoplasm, and enters the nucleus, where it initiates transcription of various target genes. Simultaneously, IQGAP1, released from the submembrane region, is upregulated and perhaps acts in the similar to active β-catenin manner. Overexpressed IQGAP1 may also stimulate activity of destabilized β-catenin.