Growing and dividing with IQGAP1

In proliferating cells, growth and division must be tightly coupled to ensure that cells maintain an appropriate size. However, many of the key proteins that maintain this coordination remain to be identified. On page 2024, Mahasin Osman and colleagues present evidence that IQGAP1 – a Cdc42 effector that has been implicated in human cancer and in exocytosis regulation – integrates cell growth and cell-cycle progression. The authors first show that expression of the C-terminal region of IQGAP1 (IQGAP1-C) promotes the proliferation and migration of cells in culture and reduces cell size. Moreover, they demonstrate that IQGAP1 phosphorylation at a residue in the C-terminus, as well as an interaction between IQGAP1 and Cdc42, are necessary for cell transformation. By contrast, the N-terminal region of IQGAP1 inhibits cytokinesis, increases cell size and impairs transformation and migration. Importantly, the N-terminus of IQGAP1 interacts with mTOR (a key cellular nutrient sensor), and this interaction is necessary for IQGAP1-mediated cell proliferation. The authors propose, therefore, that IQGAP1 acts as a phosphorylation-sensitive switch, and coordinates cell growth and division through its interactions with mTOR and Cdc42, respectively.