Nrf2 plays a critical role in the regulation of cellular oxidative stress. 
MEK-ERK activation has been shown to be one of the major pathways resulting in 
the activation of Nrf2 and induction of Nrf2 downstream targets, including phase 
II detoxifying/antioxidant genes in response to oxidative stress and 
xenobiotics. In this study, IQGAP1 (IQ motif-containing GTPase-activating 
protein 1), a new Nrf2 interaction partner that we have published previously, 
was found to modulate MEK-ERK-mediated Nrf2 activation and induction of phase II 
detoxifying/antioxidant genes. Nrf2 binds directly to the IQ domain (amino acids 
699-905) of IQGAP1. Knockdown of IQGAP1 significantly attenuated phenethyl 
isothiocyanate- or MEK-mediated activation of the MEK-ERK-Nrf2 pathway. 
Knockdown of IQGAP1 also attenuated MEK-mediated increased stability of Nrf2, 
which in turn was associated with a decrease in the nuclear translocation of 
Nrf2 and a decrease in the expression of phase II detoxifying/antioxidant genes. 
In the aggregate, these results suggest that IQGAP1 may play an important role 
in the MEK-ERK-Nrf2 signaling pathway.