Fig. 12. Model for Rho-dependent HIF-1 and angiogenesis activation during hypoxia. This schema summarizes the main steps that we have identified to play crucial roles in the induction of HIF-1 mediated by Rho GTPases. The involvement of ROS production was abolished by DPI and prevented Cdc42 and RhoA induction. Also, the C3 toxin that abolished RhoA expression prevented HIF-1 induction under hypoxic conditions. The kinetics demonstrated that Cdc42, Rac1 and RhoA are upregulated sequentially by hypoxia but it remains to be established whether there is a hierarchy of activation in Rho GTPase cascades (dotted arrows).