CDC42 GTPase cycle

Stable Identifier
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
30621321 Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases

Duan, J, Li, J, Xiao, XH, Huang, QY, Lv, LC, Qian, XL, Xiong, LX, Lai, XN

Int J Mol Sci 2019
28350208 Polarity establishment by Cdc42: Key roles for positive feedback and differential mobility

Lew, DJ, Woods, B

Small GTPases 2019
31113848 Regulation of Cdc42 and its effectors in epithelial morphogenesis

Pichaud, F, Nunes de Almeida, F, Walther, RF

J. Cell. Sci. 2019
28029388 Emerging role of Cdc42-specific guanine nucleotide exchange factors as regulators of membrane trafficking in health and disease

Polishchuk, RS, Egorov, MV

Tissue Cell 2017
29596304 Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates

Duan, J, Xiao, XH, Lv, LC, Xiong, LX, Wu, YM, He, SJ, Hu, ZZ

Molecules 2018
28571533 Cdc42 Signaling Pathway Inhibition as a Therapeutic Target in Ras- Related Cancers

Aguilar, BJ, Zhou, H, Lu, Q

Curr. Med. Chem. 2017
29858187 Targeting Rac and Cdc42 GTPases in Cancer

Maldonado, MDM, Dharmawardhane, S

Cancer Res. 2018
30754684 Focus on Cdc42 in Breast Cancer: New Insights, Target Therapy Development and Non-Coding RNAs

Zhang, Y, Li, J, Xiong, LX, Xiong, JP, Lai, XN, Jiao, XQ

Cells 2019
23406282 Reelin and the Cdc42/Rac1 guanine nucleotide exchange factor αPIX/Arhgef6 promote dendritic Golgi translocation in hippocampal neurons

Rosenberger, G, Förster, E, Meseke, M

Eur J Neurosci 2013
32322580 Targeting Rac and Cdc42 GEFs in Metastatic Cancer

Maldonado, MDM, Velazquez, L, Medina, JI, Dharmawardhane, S

Front Cell Dev Biol 2020
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