The role of Rho GTPases in disease development
Abstract
The functionality and efficacy of Rho GTPase signaling is pivotal for a plethora of biological processes. Due to the integral nature of these molecules, the dysregulation of their activities can result in diverse aberrant phenotypes. Dysregulation can, as will be described below, be based on an altered signaling strength on the level of a specific regulator or that of the respective GTPase itself. Alternatively, effector pathways emanating from a specific Rho GTPase may be under- or overactivated. In this review, we address the role of the Rho-type GTPases as a subfamily of the Ras-superfamily of small GTP-binding proteins in the development of various disease phenotypes. The steadily growing list of genetic alterations that specifically impinge on proper Rho GTPase function corresponds to pathological categories such as cancer progression, mental disabilities and a group of quite diverse and unrelated disorders. We will provide an overview of disease-rendering mutations in genes that have been positively correlated with Rho GTPase signaling and will discuss the cellular and molecular mechanisms that may be affected by them.
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GEF-catalyzed nucleotide exchange results in an active GTPase that can transduce signals to control cellular functions.
“In particular, GEF-catalyzed nucleotide exchange results in an active GTPase that can transduce signals to control cellular functions (10).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [10]
Overactivation of RHO subfamily GTPases such as RAC1 and CDC42 promotes hyperactivation of critical signaling cascades leading to cancer.
“However, overactivation of the RHO subfamily such as RAS-related C3 botulinum toxin substrate 1 (RAC1) and cell division cycle 42 homolog (CDC42) are also known to promote the hyperactivation of critical signaling cascades leading to cancer (10, 13, 17).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [10]
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- Authors
- Boettner, B., & Van Aelst, L.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 286
- Issue
- 2
- Pages
- 155-174
- ISSN
- 0378-1119 (ISSN-L)
- OpenAlex
- W2003322119
- Cited by
- 229
- References
- 11
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 10 · 2015: 6 · 2014: 8 · 2013: 11 · 2012: 17
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gene (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- Rho GTPases, Ras superfamily, small GTPases, pathogenic variants, tumor progression, mental disability, genetic alterations
- MeSH terms
- Animals, Deafness, Humans, Neoplasms, Tangier Disease, Wiskott-Aldrich Syndrome, Neurodegenerative Diseases, rho GTP-Binding Proteins
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