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Regulation of RhoA GTPase and various transcription factors in the RhoA pathway
Author(s) -
Kim JaeGyu,
Islam Rokibul,
Cho Jung Y.,
Jeong Hwalrim,
Cap KimCuong,
Park Yohan,
Hossain Abu J.,
Park JaeBong
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26487
Subject(s) - rhoa , microbiology and biotechnology , guanine nucleotide exchange factor , gtpase , small gtpase , cdc42 , phosphorylation , biology , serum response factor , actin , transcription factor , rac1 , actin cytoskeleton , signal transduction , chemistry , cytoskeleton , biochemistry , cell , gene
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.