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Review
. 2022 Apr;101(2):151209.
doi: 10.1016/j.ejcb.2022.151209. Epub 2022 Feb 10.

Fixing the GAP: The role of RhoGAPs in cancer

Gabriel Kreider-Letterman  1 , Nicole M Carr  1 , Rafael Garcia-Mata  2
Affiliations
Review

Fixing the GAP: The role of RhoGAPs in cancer

Gabriel Kreider-Letterman et al. Eur J Cell Biol. 2022 Apr.

Abstract

Cancer progression and metastasis are processes that involve significant cellular changes. Many of these changes include alterations in the activity of the Rho GTPase family of proteins. Rho GTPases are signaling proteins that function as molecular switches and are involved in the regulation of most major cellular processes. Cancer development is often associated with abnormalities in Rho GTPase signaling. Rho GTPase signaling is regulated by two families of proteins, guanine nucleotide-exchange factors (RhoGEFs) and GTPase activating proteins (RhoGAPs), that function upstream of the Rho proteins to regulate their activation and inactivation, respectively. While initial work has focused on the role of RhoGEFs in cancer, the RhoGAP family members are rapidly being established as key regulators of cancer development and progression. The aim of this review is to summarize our advances in understanding the role of RhoGAPs in cancer and to discuss their significance in the development of therapeutics.

Keywords: Cancer; Cell adhesion, cell migration; Cell invasion; Cytsokeleton; Metastasis; Oncogene; Rho GTPases; RhoGAPs; Tumor suppressor.

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Figures

Figure 1.
Figure 1.. The RhoGAP family.
The 66 RhoGAPs in the human genome were aligned using CLUSTALW to produce this phylogenetic tree. The associated diagrams show the domain composition for each member (drawn at scale). The reported Rho GTPase specificity for each RhoGAP is indicated by a colored circle in each of the tree branches. Note that the specificity characterization for the RhoGAP family is never complete, as RhoGAP assays are performed primarily on RhoA, Rac1, and Cdc42, so the specificity for the other members of the 22 known human Rho GTPases is generally not known. RhoGAPs that encode an inactive RhoGAP domain or pseudo-GAPs are indicated in magenta. For descriptions of domain abbreviations and functions, the reader is referred to the SMART website (http://smart.embl-heidelberg.de/). The figure design was inspired by a similar figure describing the DH-PH RhoGEF family designed by Rossman and colleagues (Rossman et al., 2005).
See this image and copyright information in PMC

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