IQGAPs in cancer: a family of scaffold proteins underlying tumorigenesis

Abstract

The IQGAP family comprises three proteins in humans. The best characterized is IQGAP1, which participates in protein-protein interactions and integrates diverse signaling pathways. IQGAP2 and IQGAP3 harbor all the domains identified in IQGAP1, but their biological roles are poorly defined. Proteins that bind IQGAP1 include Cdc42 and Rac1, E-cadherin, beta-catenin, calmodulin and components of the mitogen-activated protein kinase pathway, all of which are involved in cancer. Here, we summarize the biological functions of IQGAPs that may contribute to neoplasia. Additionally, we review published data which implicate IQGAPs in cancer and tumorigenesis. The cumulative evidence suggests IQGAP1 is an oncogene while IQGAP2 may be a tumor suppressor.

Figure 1

A schematic diagram of human IQGAP proteins. Domain structure (adapted from SMART and Pfam databases) and percentage amino acid identity of human IQGAP1, IQGAP2 and IQGAP3 are shown. Note the presence of four IQ motifs in IQGAP2 [3]. CHD, calponin homology domain; WW, poly-proline protein-protein domain; IQ, IQ domain (with four IQ motifs); GRD, RasGAP-related domain; RasGAP_C, carboxy-terminal sequence found in members of the IQGAP family.