Reactome | CDC42 GTPase cycle

CDC42 GTPase cycle

Stable Identifier

R-HSA-9013148

DOI

10.3180/R-HSA-9013148.2

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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