CDC42 GTPase cycle

CDC42 GTPase cycle This pathway catalogues CDC42 guanine nucleotide exchange factors (GEFs), GTPase activator proteins (GAPs), GDP dissociation inhibitors (GDIs) and CDC42 effectors. CDC42 is one of the three best characterized RHO GTPases, the other two being RHOA and RAC1. By regulating the cytoskeleton, CDC42 regulates cell polarity across different species, from yeast to humans (Pichaud et al. 2019, Woods and Lew 2019). CDC42 is an essential regulator of polarized morphogenesis in epithelial cells, where it coordinates formation of the apical membrane and lumen formation, as well as junction maturation (Pichaud et al. 2019). CDC42 plays a role in cell-to-cell adhesion and cell cycle regulation (Xiao et al. 2018). CDC42 takes part in the regulation of membrane trafficking. Dysfunction of several CDC42-specific GEFs has been shown to impair intracellular trafficking (Egorov and Polishchuk 2017). CDC42 participates in insulin synthesis and secretion and contributes to the pathogenesis of insulin resistance and diabetic nephropathy (Huang et al. 2019). CDC42 is often dysregulated in cancer because a number of GEFs and GEF activators that act upstream of RAC1 and CDC42 are known oncogenes (Aguilar et al. 2017; Maldonado et al. 2018; Zhang et al. 2019; Maldonado et al. 2020). CDC4 promotes cancer cell proliferation, survival, invasion, migration and metastasis (Xiao et al. 2018), especially under hyperglycemia (Huang et al. 2019).