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Cited by 131Protein Kinase Regulation and GTPase SignalingCellular Mechanics and InteractionsHippo pathway signaling and YAP/TAZ

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway

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Kim, Jae‐Gyu, Islam, Rokibul, Cho, Jung Y., Jeong, Hwalrim, Cap, Kim‐Cuong, Park, Yohan, Hossain, Abu J., Park, Jae‐Bong·2018·Journal of Cellular Physiology
DOI 10.1002/jcp.26487PMC PMC13482483
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Abstract

RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA‐RhoGDI complex exists in the cytosol and the active GTP‐bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA‐GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA‐RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c‐Myc, HIF‐1α/2α, Stat 6, and NF‐κB along with several reported microRNAs. As the role of RhoA in regulating actin‐filament formation and myosin‐actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F‐actin)‐dependent (“actin switch”) or—independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP‐1, NF‐κB, YAP/TAZ, β‐catenin, and hypoxia inducible factor (HIF)‐1α. Interestingly, RhoA also itself is localized to the nucleus by an as‐yet‐undiscovered mechanism.

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  • Several transcription factors regulate RHOA expression, including c-Myc, Max, HIF-1α, NF-κB, and STAT6, together with several miRNAs.

    “Several transcription factors have been shown to regulate RHOA expression, including c-Myc, Max, hypoxia-inducible factor 1 alpha (HIF-1α), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription 6 (STAT6), together with several reported miRNAs (Figure 2C) [82,83].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [82]

    The Abstract and sections 2.3–2.4 support regulation of RhoA expression by c-Myc, HIF-1α, NF-κB, STAT6, and several miRNAs. The passages on transcriptional regulation describe a Myc–Skp2–Miz1–p300 complex, but do not identify Max as a regulator of RhoA expression. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Other transcription factors regulated by RhoA include PPARγ, β-catenin, STAT3, and HIF-1α.

    “Other transcription factors regulated by RhoA include peroxisome proliferator-activated receptor γ (PPARγ), β-catenin, signal transducer and activator of transcription-3 (STAT3), and hypoxia inducible factor-1α (HIF-1α).”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [82]

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Cited by

Sorted by citations

Authors
Kim, J., Islam, R., Cho, J. Y., Jeong, H., Cap, K., Park, Y., Hossain, A. J., & Park, J.
Affiliations
Hallym University (KR)
Corresponding author
Park, Jae‐Bong
ORCID
Venue
Journal of Cellular Physiology
Publisher
Wiley
Published
2018-03-25
Volume
233
Issue
9
Pages
6381-6392
ISSN
  • 0021-9541 (ISSN-L)
  • 1097-4652
DOI
10.1002/jcp.26487
PMC
PMC13482483
OpenAlex
W2791645463
Cited by
131
References
0
Citations by year
2026: 8 · 2025: 13 · 2024: 16 · 2023: 21 · 2022: 19 · 2021: 23 · 2020: 19 · 2019: 9 · 2018: 3
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cellular Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
Hallym University (HRF‐201303‐017)
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 Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
RhoA GTPase, guanine nucleotide exchange factor, GTPase-activating protein, guanine nucleotide dissociation inhibitor, transcriptional regulation, c-Myc, HIF-1α, STAT6, NF-κB, microRNA, serum response factor, AP-1, YAP/TAZ, β-catenin, hypoxia-inducible factor, cytoskeleton regulation
MeSH terms
Actins, Animals, Cytosol, Humans, Transcription Factors, Transcription, Genetic, NF-kappa B, rhoA GTP-Binding Protein

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