Affinage

RND3

Rho-related GTP-binding protein RhoE · UniProt P61587

Length
244 aa
Mass
27.4 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RND3/RhoE is an atypical Rho-family protein that, unlike classical Rho GTPases, is constitutively GTP-bound and GTPase-deficient, acting as a negative regulator of RhoA-ROCK signaling to drive actin stress fiber disassembly and remodel cell shape, migration, and survival (PMID:9671486, PMID:12009891). Its constitutive GTP-bound state arises from substitution of the catalytic glutamine and switch-II serines that prevent GTP hydrolysis (PMID:12009891). The central effector mechanism is direct binding to ROCK I (but not ROCK II), engaging the kinase domain N-terminal region at a site distinct from the RhoA-binding site to block phosphorylation of myosin light chain phosphatase and disassemble stress fibers (PMID:12773565); structural and domain-mapping work defined a bipartite interaction in which an effector-region contact mediates inhibition while a separate C-lobe αG-helix contact positions RND3 for multi-site phosphorylation by ROCK I, and N-terminal ROCK I dimerization is required for binding (PMID:18946488, PMID:18215121). RND3 also activates p190RhoGAP by targeting it to lipid rafts via its N-terminal KERRA sequence, providing a parallel route to RhoA suppression (PMID:22357615). Beyond ROCK inhibition, RND3 exerts ROCK-independent anti-proliferative effects by blocking mTOR-independent 4E-BP1 phosphorylation, thereby restraining cap-dependent translation of cyclin D1 and c-Myc and inhibiting cell-cycle progression and Ras/Raf-induced transformation (PMID:15340047, PMID:19850923). RND3 additionally functions as a scaffold for protein turnover and transcriptional control: it promotes ubiquitination and degradation of the Notch intracellular domain and of Snail1 to suppress Notch signaling and migration (PMID:23630292, PMID:27705942), and sequesters NF-κB p65/p50 subunits in the cytosol to block their nuclear translocation and dimerization (PMID:30586715). RND3 activity is tightly regulated post-translationally—by ROCK I phosphorylation at Ser11 that enhances stability and cytosolic localization (PMID:15775972), PKCα phosphorylation that redirects membrane targeting (PMID:19723022), farnesylation-dependent membrane association (PMID:14561824), and Skp2-mediated proteasomal degradation at Lys235 (PMID:24045951)—and transcriptionally by p53 under genotoxic stress, where RND3 inhibits ROCK I-mediated apoptosis to promote survival (PMID:17174923). Through these activities RND3 governs diverse physiological processes including keratinocyte differentiation, cortical neuron migration, myoblast fusion, osteoclast podosome dynamics, and cardiac stress responses (PMID:23630292, PMID:24572910, PMID:24284899, PMID:18369372, PMID:18923151); in mice, Rnd3 deletion causes hydrocephalus via enhanced Notch signaling (PMID:23630292).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Established that RhoE is an atypical Rho protein that is constitutively GTP-bound rather than cycling, and that it antagonizes RhoA by disassembling stress fibers and increasing migration—inverting the canonical Rho phenotype.

    Evidence Biochemical GTP/GDP binding and GTPase assays plus microinjection and migration readouts in macrophages and MDCK cells

    PMID:9671486

    Open questions at the time
    • Did not identify the direct molecular target through which RhoE antagonizes RhoA
    • Mechanism of constitutive GTP-loading not yet structurally explained
  2. 2002 High

    Provided the structural basis for the constitutive GTP-bound state, answering why RND3 cannot hydrolyze GTP.

    Evidence X-ray crystallography of the RhoE G-domain bound to GTP/Mg2+ at 2.1 Å

    PMID:12009891

    Open questions at the time
    • Structure of the core domain alone does not reveal effector engagement
    • Does not address regulation by phosphorylation or localization
  3. 2003 High

    Identified ROCK I as the direct effector target, defining the central molecular mechanism by which RhoE inhibits RhoA-driven contractility.

    Evidence Reciprocal co-IP of endogenous proteins, colocalization on trans-Golgi, and ROCK I activity readouts (MLC phosphatase phosphorylation, stress fibers)

    PMID:12773565

    Open questions at the time
    • Did not resolve the structural binding interface
    • Selectivity for ROCK I over ROCK II mechanistically unexplained at the time
  4. 2004 High

    Demonstrated a ROCK-independent anti-proliferative function, showing RhoE blocks cell-cycle progression at the pRb checkpoint without altering canonical mitogenic kinases.

    Evidence Inducible RhoE expression with BrdU/flow cytometry, cyclin D1/p21 blotting, and E7/E1A/cyclin E epistatic rescue

    PMID:15340047

    Open questions at the time
    • The molecular target mediating cyclin D1 loss was not identified
    • Distinction from ROCK pathway left mechanistically incomplete
  5. 2005 High

    Established phosphoregulation of RhoE, showing ROCK I phosphorylates RhoE at Ser11 to increase stability and shift it to the cytosol, creating a feedback layer on its own inhibitory activity.

    Evidence In vitro kinase assays, phospho-specific antibodies, fractionation, and PDGF/PKC stimulation in cells

    PMID:15775972 PMID:16042565

    Open questions at the time
    • Number and identity of all phosphosites beyond Ser11 not fully resolved
    • Functional consequence of each individual site not separated
  6. 2008 High

    Resolved the RhoE:ROCK I structure and showed inhibition and phosphorylation occur through distinct contacts, while PDK1 competition and ROCK I dimerization gate the interaction.

    Evidence Co-crystal structure with mutagenesis, plus siRNA depletion and binding competition assays

    PMID:18204440 PMID:18215121 PMID:18946488

    Open questions at the time
    • The effector-region partner mediating actin disassembly was not identified
    • How phosphorylation feeds back onto the structural interface in vivo not fully defined
  7. 2009 High

    Identified the molecular basis of RhoE's ROCK-independent growth inhibition as mTOR-independent blockade of 4E-BP1 phosphorylation, restraining cap-dependent translation of cyclin D1 and c-Myc.

    Evidence Cap pull-down, 4E-BP1/eIF4E interaction blots, mTOR/Raptor co-IP, and eIF4E genetic rescue of transformation

    PMID:19850923

    Open questions at the time
    • The proximal RhoE target upstream of 4E-BP1 was not identified
    • Connection to the constitutive GTP-bound state unclear
  8. 2009 High

    Showed PKCα directly phosphorylates Rnd3 to control its internal-membrane localization and ROCK-pathway inhibitory capacity, adding a second kinase regulatory input.

    Evidence In vitro PKCα kinase assay, PKCα-null cells, and non-phosphorylatable mutant with fractionation

    PMID:19723022

    Open questions at the time
    • PKCα phosphosites not precisely mapped relative to ROCK I sites
    • Interplay between PKCα and ROCK I phosphorylation unresolved
  9. 2012 Medium

    Explained Rnd-family functional specificity in RhoA inhibition by identifying the N-terminal KERRA lipid-raft targeting sequence required for p190RhoGAP activation.

    Evidence N-terminal mutation analysis, lipid raft fractionation, and p190RhoGAP activity assays

    PMID:22357615

    Open questions at the time
    • Single-lab domain mapping not independently confirmed
    • How raft localization couples mechanistically to GAP activation not detailed
  10. 2013 High

    Established RND3 as a degradation scaffold in Notch signaling, promoting NICD ubiquitination via FBW7 to suppress Notch transcription, with in vivo loss causing hydrocephalus.

    Evidence Reciprocal co-IP, ubiquitination assays, knockout mice with pharmacological Notch-inhibition rescue

    PMID:23630292

    Open questions at the time
    • How a GTPase-fold protein scaffolds the ubiquitin machinery structurally unknown
    • Relationship to RhoE's actin-regulating function unclear
  11. 2013 High

    Defined RhoE as the upstream regulator of a ROCK-cofilin axis controlling actin turnover across cell types, integrating its function into tissue-level processes.

    Evidence Primary knockout/knockdown cells (osteoclasts, radial glia, myoblasts) with cofilin readouts and active-cofilin or RhoA/ROCK inhibitor rescue

    PMID:18369372 PMID:23535656 PMID:24284899

    Open questions at the time
    • Tissue-specific differences in RhoE output not mechanistically reconciled
    • Quantitative thresholds of RhoA inhibition needed in each context undefined
  12. 2014 Medium

    Expanded RhoE's regulatory roles to membrane-receptor turnover and migration control, showing it routes β2-AR to lysosomal degradation and degrades Snail1, while plexin-B2 antagonizes its RhoA-inhibitory function.

    Evidence Knockout mice, ubiquitination assays, in utero electroporation, competition binding, and co-IP

    PMID:24525741 PMID:24572910 PMID:25348166 PMID:27705942

    Open questions at the time
    • Whether RhoE acts catalytically or stoichiometrically in degradation pathways unresolved
    • Some interactions rest on single-lab co-IP
  13. 2019 High

    Established a transcription-factor sequestration mechanism, with RhoE binding p65/p50 to block NF-κB nuclear translocation and heterodimerization, defining a cardioprotective anti-inflammatory role.

    Evidence BiFC, co-IP, EMSA, and cardiomyocyte-specific genetic models in a myocardial infarction setting

    PMID:30586715

    Open questions at the time
    • Structural basis of p65 dimerization-domain occupancy not solved
    • Relationship to RhoE's GTP-bound conformation unknown
  14. 2023 Medium

    Extended RhoE's ubiquitin-editing activity to TRAF6, showing it shifts TRAF6 from K63- to K48-linked ubiquitination to suppress NF-κB and endothelial pyroptosis.

    Evidence LC-MS/MS, co-IP, molecular docking, linkage-specific ubiquitination assays, and endothelial Rnd3 mouse models with TRAF6-knockdown rescue

    PMID:37743632

    Open questions at the time
    • Direct enzymatic versus scaffolding role in ubiquitin-linkage switching not distinguished
    • Single-lab finding awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RND3's single constitutively GTP-bound G-domain mechanistically partitions among its many divergent outputs—ROCK I inhibition, translational control, ubiquitin-mediated degradation of NICD/Snail1/TRAF6, and transcription-factor sequestration—remains unresolved.
  • No structural model explains how one G-domain scaffolds ubiquitin ligases versus binding ROCK I
  • The branch point determining ROCK-dependent versus ROCK-independent outputs in a given cell is undefined
  • Whether degradation-promoting interactions require the effector loop or distinct surfaces is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0003924 GTPase activity 2 GO:0060089 molecular transducer activity 2 GO:0140313 molecular sequestering activity 1
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 3
Partners
NICDPDK1PLXNB2RELAROCK1SKP2SNAIL1TRAF6

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 RhoE binds directly to ROCK I (but not ROCK II or other RhoA targets tested), interacting with the amino-terminal kinase domain region of ROCK I at a site distinct from the RhoA-binding site. This interaction was confirmed by co-immunoprecipitation of endogenous proteins, and RhoE and ROCK I co-localized on the trans-Golgi network. RhoE overexpression inhibited ROCK I-induced stress fiber formation and phosphorylation of myosin light chain phosphatase, demonstrating that RhoE induces stress fiber disassembly by directly binding and inhibiting ROCK I. Co-immunoprecipitation of endogenous proteins, colocalization imaging, overexpression with ROCK I activity readouts (MLC phosphatase phosphorylation, stress fiber formation) Molecular and cellular biology High 12773565
1998 RhoE (mouse) binds GTP but does not detectably bind GDP and has low intrinsic GTPase activity. Microinjection of RhoE in macrophages and MDCK cells induced actin reorganization and complete disappearance of stress fibers, while RhoE localized to lateral membranes of MDCK cells. RhoE increased migration speed of HGF-stimulated MDCK cells, in contrast to RhoA inhibition of migration. Biochemical GTP/GDP binding assays, GTPase activity assays, microinjection, immunofluorescence, migration assays Molecular and cellular biology High 9671486
2002 Crystal structure of RhoE/Rnd3 core G-protein domain in complex with GTP and Mg2+ at 2.1 Å resolution revealed that serines at positions equivalent to Ala59 and Gln61 in Ras account for the lack of GTP hydrolysis: the absent conserved glutamine raises the transition state energy, and the serines stabilize the GTP-bound switch II conformation and may prevent catalytic water positioning. X-ray crystallography at 2.1 Å resolution Biochemistry High 12009891
2005 ROCK I phosphorylates RhoE on multiple residues in vitro. In cells, ROCK I-phosphorylated RhoE localizes to the cytosol whereas unphosphorylated RhoE is membrane-associated. Phosphorylation does not affect RhoE binding to ROCK I but increases RhoE protein stability. Using phospho-specific antibodies, ROCK I was shown to phosphorylate endogenous RhoE at serine 11 upon PDGF stimulation, and this phosphorylation requires active PKC signaling. Phosphorylation correlates with RhoE's ability to induce stress fiber disruption and inhibit Ras-induced transformation. In vitro kinase assay, phospho-specific antibodies, subcellular fractionation, cell stimulation assays, protein stability measurements The EMBO journal High 15775972
2008 Crystal structure of RhoE in complex with the ROCK I kinase domain at high resolution revealed that RhoE interacts with the C-lobe αG helix of ROCK I via a novel binding site remote from its effector region, positioning its N and C termini proximal to the ROCK I catalytic site to enable multi-site phosphorylation. Disruption of the ROCK I:RhoE interface abolished RhoE phosphorylation but had no effect on RhoE-mediated stress fiber disassembly. Mutation of the RhoE effector region attenuated actin cytoskeleton disruption, indicating RhoE exerts inhibitory effects on ROCK I through protein(s) binding its effector region. X-ray crystallography, site-directed mutagenesis, functional actin cytoskeleton assays The EMBO journal High 18946488
2008 PDK1 competes directly with RhoE for binding to ROCK1 at the plasma membrane in a non-catalytic manner. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility. PDK1 depletion alters ROCK1 localization and reduces its ability to drive cortical acto-myosin contraction. siRNA depletion, direct binding competition assays, localization imaging, MLC phosphorylation readouts, in vivo motility assays Nature cell biology High 18204440
2004 RhoE expression inhibits cell cycle progression and serum-induced S-phase entry. RhoE-expressing cells failed to accumulate cyclin D1 or p21(cip1) protein or activate E2F-regulated genes despite normal ERK, PI3K/Akt, FAK, and Rac activation. Expression of proteins bypassing the pRb checkpoint (HPV E7, adenovirus E1A, cyclin E) rescued cell cycle progression. RhoE also inhibited Ras- and Raf-induced fibroblast transformation. Neither ROCK nor RhoA inhibition accounted for the cell cycle response. Inducible RhoE expression system, BrdU/flow cytometry cell cycle analysis, western blotting for cyclin D1/p21/Rb, epistasis with E7/E1A/cyclin E rescue Molecular and cellular biology High 15340047
2000 Raf activation downstream of oncogenic Ras induces expression of Rnd3 (via the MEK/ERK pathway), which acts as an endogenous inhibitor of Rho function to cause loss of actin stress fibers without reducing Rho-GTP levels. Expression of Rnd3 alone at levels equivalent to Raf transformation caused substantial loss of actin stress fibers. Pharmacological MEK inhibition prevented Rnd3 induction and preserved stress fibers. Conditional Raf activation, Rho pull-down GTP-loading assay, Rnd3 overexpression, MEK inhibitor treatment, actin immunofluorescence Molecular and cellular biology High 11094087
2000 A novel Staphylococcus aureus C3-like ADP-ribosyltransferase (C3Stau) modifies RhoE and Rnd3 by ADP-ribosylation at Asn-44 (equivalent to Asn-41 in RhoA), in addition to RhoA. This was confirmed in vitro with recombinant proteins and in vivo in Xenopus laevis oocytes expressing RhoE. In vitro ADP-ribosylation assay with recombinant proteins, in vivo modification in Xenopus oocytes, cloning of C3Stau from genomic DNA The Journal of biological chemistry High 11124969
2006 RhoE is a transcriptional target of p53. Genotoxic stress triggers p53-dependent RhoE induction, which causes actin stress fiber disassembly. RhoE inhibits ROCK I activity during genotoxic stress and thereby suppresses apoptosis. Silencing of RhoE induction in response to genotoxic stress increased apoptosis, indicating RhoE promotes cell survival by inhibiting ROCK I-mediated apoptosis. siRNA knockdown, luciferase reporter assays for p53-dependent RhoE transcription, ROCK I activity assays, apoptosis measurements, stress fiber immunofluorescence Current biology : CB High 17174923
2009 PKCα directly phosphorylates Rnd3 in vitro and in cells (upon PKC agonist stimulation). PKCα-mediated phosphorylation causes an electrophoretic mobility shift and enrichment of Rnd3 at internal membranes. This does not occur in PKCα-null cells or with a non-phosphorylatable Rnd3 mutant. PKCα phosphorylation affects Rnd3's ability to block Rho-ROCK pathway signaling. In vitro kinase assay with PKCα, PKCα-null cells, non-phosphorylatable Rnd3 mutant, subcellular fractionation, ROCK pathway readouts The Biochemical journal High 19723022
2008 N-terminus-mediated dimerization of ROCK I is required for RhoE binding. The central coiled-coil domain can dimerize ROCK I but is insufficient without the N-terminus to allow RhoE binding. ROCK I kinase activity is required for N-terminal dimerization and RhoE binding, although inclusion of part of the coiled-coil domain can compensate for lack of kinase activity. N-terminus-mediated dimerization is also required for ROCK I to induce stellate actin stress fibers in cells. ROCK I domain deletion mutants, dimerization assays, RhoE binding assays, kinase-dead mutants, actin stress fiber formation assays in cells The Biochemical journal Medium 18215121
2009 RhoE inhibits phosphorylation of the translational repressor 4E-BP1 in response to extracellular stimuli independently of mTOR (S6K phosphorylation, mTOR/Raptor association unaffected by RhoE). RhoE prevents release of eIF4E from 4E-BP1, thereby inhibiting cap-dependent translation. This mechanism explains RhoE-mediated inhibition of cyclin D1 translation and c-Myc expression. eIF4E overexpression rescued cell cycle progression and Ras-induced transformation in RhoE-expressing cells. Western blotting for 4E-BP1/eIF4E interaction (cap pull-down), S6K phosphorylation, mTOR/Raptor co-IP, eIF4E rescue experiments, transformation assays The Journal of biological chemistry High 19850923
2012 Rnd1 and Rnd3, but not Rnd2, contain a KERRA sequence in their N-terminus that functions as a lipid raft-targeting determinant. Lipid raft targeting is required for p190 RhoGAP activation by Rnd1 and Rnd3. This mechanism accounts for the functional difference between Rnd proteins in RhoA inhibition signaling despite all three Rnd proteins binding p190 RhoGAP equally in vitro. N-terminal deletion/mutation analysis, lipid raft fractionation, p190 RhoGAP activity assay Molecular biology of the cell Medium 22357615
2010 Rnd3 binds to the RhoA GEF Syx (synectin-binding RhoA exchange factor) identified by unbiased two-step affinity purification and mass spectrometry. The Syx interaction with Rnd3 occurs through a region similar to the Raf1 Ras-binding domain (RBD), not via the Syx DH domain. Rnd3 negatively regulates Syx activity in vivo, as shown by zebrafish morpholino knockdown rescue experiments where a Rnd3-binding defective Syx mutant (E164A/R165D) was more potent at rescuing embryonic defects than wild-type Syx. Affinity purification/mass spectrometry, domain mutation binding assays, zebrafish morpholino knockdown, mRNA rescue with wild-type vs. Rnd3-binding mutant PloS one Medium 20811643
2013 Rnd3 interacts physically with the Notch intracellular domain (NICD), promotes NICD ubiquitination, and facilitates protein degradation of NICD, CSL, and MAML1 (components of the Notch transcriptional complex). Rnd3 facilitates binding of NICD to FBW7 (ubiquitin ligase) to enhance NICD degradation, thereby inhibiting Notch transcriptional activity. In mice, Rnd3 genetic deletion caused hydrocephalus through decreased NICD protein degradation and enhanced Notch signaling, which was rescued by Notch inhibition. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, genetic knockout mice, pharmacological Notch inhibition rescue Proceedings of the National Academy of Sciences of the United States of America High 23630292
2014 Rnd3 downregulation attenuates β2-adrenergic receptor (β2-AR) lysosomal targeting and ubiquitination, leading to elevated β2-AR protein levels and hyperactivation of PKA signaling. PKA activation destabilizes ryanodine receptor type 2 (RyR2) channels, causing severe Ca2+ leakage. Rnd3-null mouse embryos showed fetal arrhythmias; PKA inhibitor treatment curtailed irregular Ca2+ release. Rnd3 knockout mice, neonatal cardiomyocyte knockdown, β2-AR ubiquitination assays, PKA activity/cAMP measurements, Ca2+ imaging, PKA inhibitor rescue Circulation research High 25348166
2014 Plexin B2 physically interacts with Rnd3 and competes with p190RhoGAP for Rnd3 binding, blocking Rnd3-mediated inhibition of RhoA. Plexin B2 also recruits RhoGEFs to directly stimulate RhoA activity. This antagonistic interaction determines the level of RhoA activity appropriate for cortical neuron migration in the embryonic cerebral cortex. Co-immunoprecipitation, in utero electroporation of cortical neurons, RhoA activity assays, competition binding assays Nature communications High 24572910
2014 RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated Notch1 intracellular domain (N1IC) through interaction with importins. RhoE is itself a transcriptional target of activated Notch1. RhoE depletion renders primary keratinocytes resistant to Notch1-mediated differentiation. RhoE is essential for recruitment of N1IC to promoters of Notch1 target genes, establishing a regulatory feedback loop. Co-immunoprecipitation with importins, chromatin immunoprecipitation, siRNA knockdown, luciferase reporter assays, keratinocyte differentiation assays Cancer research Medium 24525741
2016 RND3 physically interacted with Snail1 protein, enhanced Snail1 ubiquitination, and facilitated its proteasomal degradation. Forced RND3 expression inhibited Snail1 transcriptional activity, blocking glioblastoma cell migration and invasion. RND3 downregulation augmented Snail1 activity and decreased E-cadherin expression, promoting invasion; this was attenuated by Snail1 knockdown. Co-immunoprecipitation, ubiquitination assays, RND3 overexpression and knockdown, in vitro migration/invasion assays, in vivo GBM xenograft Oncotarget Medium 27705942
2016 Rnd3 physically interacted with HIF1α and stabilized it, consequently promoting VEGFA expression and endothelial cell tube formation. In Rnd3 haploinsufficient mice, stressed hearts showed impaired angiogenesis and decreased HIF1α and VEGFA expression; this was partially rescued by CoCl2 (a HIF1α stabilizer), confirming Rnd3's role in stress-responsive angiogenesis through the HIF1α-VEGFA pathway. Co-immunoprecipitation, Rnd3 knockout/transgenic mice, transverse aortic constriction model, CoCl2 pharmacological rescue, angiogenesis assays Hypertension Medium 26781283
2019 RhoE interacts with p65 and p50 NF-κB subunits individually in the cytosol, blocks their nuclear translocation, and also occupies the dimerization domain of p65 to disrupt p65/p50 heterodimerization. This was demonstrated by bimolecular fluorescence complementation, co-immunoprecipitation, and EMSA. Cardiac RhoE overexpression inhibited NF-κB activity, restrained post-MI inflammation, and improved cardiac function and survival. Bimolecular fluorescence complementation, co-immunoprecipitation, electrophoretic mobility shift assay (EMSA), genetic mouse models (cardiomyocyte-specific overexpression/haploinsufficiency), MI model Circulation High 30586715
2013 In osteoclasts, RhoE is indispensable for migration and bone resorption by maintaining fast actin turnover in podosomes. RhoE activates the actin depolymerizing protein cofilin by inhibiting its ROCK-mediated phosphorylation. Primary RhoE-deficient osteoclasts showed dysfunctional sealing zones and impaired podosome patterning, establishing a RhoE-ROCK-cofilin pathway for podosome dynamics. Primary RhoE-deficient osteoclast isolation, bone resorption assays, actin turnover imaging, cofilin phosphorylation western blotting, ROCK inhibitor experiments Molecular biology of the cell Medium 24284899
2013 Rnd3 silencing in embryonic cerebral cortex radial glial progenitors disrupts interkinetic nuclear migration, apical attachment, and orientation of cleavage plane through actin-dependent mechanisms. These defects were rescued by co-expression of constitutively active cofilin, demonstrating that Rnd3-mediated actin filament disassembly coordinates radial glial cell behavior. Additionally, Rnd3 limits basal progenitor divisions via suppression of cyclin D1 translation through a distinct actin-independent mechanism. In utero electroporation, constitutively active cofilin rescue, siRNA knockdown, cell cycle analysis, cyclin D1 translation assays Nature communications High 23535656
2013 RhoE is required for myoblast elongation and alignment before fusion. RhoE-deficient myoblasts show defective p190RhoGAP activation and failure to inhibit RhoA at the onset of fusion. RhoE also interacts with ROCK I, whose activity must be downregulated to allow fusion. Pharmacological inactivation of RhoA or ROCK restored myoblast fusion in RhoE-deficient cells, establishing RhoE's role upstream of p190RhoGAP-RhoA-ROCK I in myoblast fusion. RhoE siRNA knockdown in C2C12 cells, p190RhoGAP activity assay, RhoA activity assay, co-immunoprecipitation with ROCK I, pharmacological RhoA/ROCK inhibition rescue Cell death and differentiation High 18369372
2005 RhoE is farnesylated and localizes partly on membranes (including Golgi and plasma membrane) and in the cytosol. ROCK I-mediated phosphorylation reduces RhoE membrane association and correlates with its activity in inducing stress fiber disruption. RhoE also acts independently of ROCK to inhibit cell cycle progression, in part by preventing translation of cyclin D1. Farnesylation inhibitor treatment, subcellular fractionation, phospho-mutant analysis, ROCK inhibitor experiments, cyclin D1 translation assays Biochemical Society transactions Medium 16042565
2012 RhoE-deficient neurons exhibit decreased neurite number and length, reduced axon outgrowth, and delayed neuronal polarization. These defects involve the RhoA/ROCK/LIMK/cofilin signaling pathway, as evidenced by altered cofilin phosphorylation in RhoE-null hippocampal neurons. RhoE knockout hippocampal neuron cultures, neurite morphology analysis, cofilin/LIMK phosphorylation western blotting Journal of neurochemistry Medium 22428561
2003 Rnd3 upregulation in mid-pregnant rabbit myometrium correlates with inhibition of RhoA-Rho kinase-mediated Ca2+ sensitization. Treatment with farnesyl-transferase inhibitor manumycin A (blocking Rnd3 membrane targeting) restored RhoA-Rho kinase-dependent Ca2+ sensitization in mid-pregnant myometrium, establishing Rnd3 farnesylation as mechanistically required for its inhibition of myometrial contractility. Differential gene expression screening (cDNA array), protein expression western blotting, permeabilized smooth muscle contractility assays, farnesyl-transferase inhibitor treatment The Journal of physiology Medium 14561824
2013 The RhoE/ROCK/ARHGAP25 signaling pathway controls cell invasion: RhoE expression is low in alveolar rhabdomyosarcoma (ARMS), and its overexpression reduces invasion potential. ROCK (regulated by RhoE) activates ARHGAP25, a GAP for Rac, which is required downstream of ROCK II for ARMS cell invasion. This defines a RhoE→ROCK→ARHGAP25→Rac inhibition pathway promoting invasive potential. 3D spheroid invasion assay, RhoE overexpression/knockdown, ROCK II inhibition, ARHGAP25 knockdown, Rac activity assay Molecular biology of the cell Medium 27413008
2016 A RhoA-ROCK-Rnd3 feedback loop determines local sites of actin cortex reassembly during membrane blebbing. Live-cell imaging revealed that Eps8 and activated ezrin mark foci where local actin reassembly occurs in blebs, and this process is regulated by the RhoA-ROCK-Rnd3 circuit. Live-cell imaging of GFP-actin, fluorescent Eps8 and ezrin reporters, ROCK inhibitor treatment, Rnd3 manipulation Proceedings of the National Academy of Sciences of the United States of America Medium 26976596
2012 Rnd3 knockdown in HCC cells increased cell motility and invasiveness. Stable Rnd3 knockdown enhanced phosphorylation of myosin phosphatase targeting subunit (MYPT1), promoted stress fiber assembly, and increased plasma membrane blebbing, all consistent with activation of the Rho/ROCK pathway. In vivo, Rnd3 knockdown enhanced local invasion of HCC cells with increased venous invasion. Lentiviral shRNA knockdown, in vitro motility/invasion assays, MYPT1 phosphorylation western blot, orthotopic liver injection mouse model, histological analysis Hepatology Medium 22829315
2013 RhoE interacts with Skp2 (an F-box protein/E3 ubiquitin ligase component). RhoE protein levels are regulated by proteasomal degradation: RhoE accumulates in G1 and decreases at the G1/S transition, with a half-life shorter than other Rho proteins. The Skp2-interacting domain maps to amino acids 231-240 of RhoE, and Lys235 is the ubiquitylation substrate. Skp2 overexpression decreases both RhoE and p27 levels. Co-immunoprecipitation with Skp2, proteasome inhibitor treatment, protein half-life measurements, domain mapping with deletion mutants, Lys235 site-directed mutagenesis, flow cytometry cell cycle analysis The Journal of biological chemistry High 24045951
2012 RhoE is regulated by cyclic AMP/PKA signaling in trophoblast cells: treatment with cAMP analogue dbcAMP strongly upregulated RhoE, and this was mediated through PKA (blocked by PKA-specific inhibitor PKI and mimicked by N6-phenyl-cAMP). RhoE silencing by RNAi significantly decreased dbcAMP-induced BeWo cell fusion without affecting differentiation markers. PKA-specific cAMP analogues, PKA inhibitor (14-22 amide), RNAi knockdown, fusion index quantification, HCG/PLAP differentiation markers PloS one Medium 22272352
2016 Rnd3 in endothelial cells acts through RhoB: Rnd3 overexpression increases RhoB expression, which is then required for Rnd3-induced stress fiber assembly (a response opposite to other cell types). Rnd3 does not act through known signaling partners (p190RhoGAP, ROCK, Syx) in endothelial cells and does not need membrane association to increase stress fibers. Rnd3 overexpression, RhoB knockdown, dominant-negative and constitutively active mutants, actin immunofluorescence, RhoB expression western blotting Biology open Medium 23430146
2016 Rnd3 interacts with plexin-B2 preferentially over plexin-B1 and -B3 (shown by immunoprecipitation). Plexin-B2 promotes Rnd3-induced cell rounding and loss of stress fibers, and enhances Rnd3-mediated inhibition of HeLa cell invasion. Specific amino acids in Rnd3 required for plexin-B2 interaction were identified; mutation of these residues prevents Rnd3-induced morphological changes. Co-immunoprecipitation, site-directed mutagenesis of Rnd3:plexin-B2 interface, cell rounding assays, invasion assays Journal of cell science Medium 27656111
2014 Rnd3 downregulation in Rnd3 haploinsufficient mice leads to elevated ROCK kinase activity, remarkable apoptosis, and increased caspase-3 in hearts under pressure overload. Pharmacological ROCK inhibition (fasudil) partially improved cardiac function. Genetic deletion of ROCK1 in Rnd3 haploinsufficient mice (Rnd3+/-/ROCK1-/-) partially but not completely rescued heart failure, indicating ROCK1-dependent and -independent mechanisms for Rnd3-mediated cardiac protection. Haploinsufficient Rnd3+/- mice, transverse aortic constriction, ROCK1 double-knockout, fasudil pharmacological treatment, caspase-3 activity, cardiac function echocardiography Cell death & disease Medium 24901055
2018 Restoration of Rnd3 levels in IPF fibroblasts increases p190RhoGAP activity and decreases RhoA activity, reducing the fibrotic phenotype. IPF drugs nintedanib and pirfenidone decrease RhoA activity and fibrotic phenotype by upregulating Rnd3 expression and p190RhoGAP activity, establishing a Rnd3→p190RhoGAP→RhoA pathway in IPF. Rnd3 re-expression in IPF fibroblasts, p190RhoGAP activity assay, RhoA activity assay, pharmacological drug treatment, fibrosis phenotype assays Molecular biology of the cell Medium 29995590
2021 Rnd3 physically interacts with PPARγ and promotes the PPARγ-UCP2 signaling cascade. Loss of Rnd3 in trophoblasts leads to excessive ROS, mitochondrial injury, and proton leakage; forced expression of PPARγ rescues Rnd3 deficiency-mediated mitochondrial dysfunction. This defines a Rnd3-PPARγ-UCP2 pathway regulating placental mitochondrial ROS. Co-immunoprecipitation, ROS/mitochondrial function assays, Rnd3 overexpression/knockdown in primary PE trophoblasts, PPARγ overexpression rescue FASEB journal Medium 34046947
2023 Rnd3 directly interacts with the ring finger domain of TRAF6, suppresses K63-linked TRAF6 ubiquitination, and promotes K48-linked TRAF6 ubiquitination, thereby inhibiting NF-κB activation and promoting TRAF6 degradation. This was established by LC-MS/MS, Co-IP, and molecular docking. TRAF6 knockdown countered Rnd3 knockout-induced EC pyroptosis in vivo and in vitro. LC-MS/MS, co-immunoprecipitation, molecular docking, K63/K48 ubiquitination assays, endothelium-specific Rnd3 transgenic/knockout mice, TRAF6 knockdown rescue Clinical and translational medicine Medium 37743632
2025 Rnd3 directly binds ROCK1 in the cytoplasm and inhibits ROCK1-induced Drp1 phosphorylation at Ser616, thereby inhibiting mitochondrial fission and PANoptosis (apoptosis, pyroptosis, necroptosis) in doxorubicin-induced cardiotoxicity. ROCK1 knockdown nullified the cardioprotective effects of Rnd3. This was established by co-immunoprecipitation, protein-protein docking, and cardiomyocyte-specific transgenic/knockout models. Co-immunoprecipitation, protein-protein molecular docking, Drp1 Ser616 phosphorylation assays, cardiomyocyte-specific Rnd3-Tg and Rnd3LSP/LSP mice, ROCK1 siRNA knockdown Cell death & disease Medium 39755713
2022 In cardiac fibroblasts, Rnd3 regulates Notch signaling by interacting with NICD and regulates TGF-β signaling by interacting with ROCK1. Fibroblast-specific Rnd3 overexpression suppressed Notch and TGF-β signaling, attenuated cardiac oxidative stress and fibrosis. Glucotoxicity and lipotoxicity control Rnd3 expression by regulating binding of nuclear receptor Nr1H2 to the Rnd3 promoter (established by ChIP). Co-immunoprecipitation (NICD and ROCK1), RNA sequencing, ChIP assay (Nr1H2 binding to Rnd3 promoter), fibroblast-specific Rnd3 knockout and transgenic mice, in vitro fibroblast assays Theranostics Medium 36438502
2019 RND3 knockdown in primary human adipocytes reduces cAMP- and isoproterenol-induced lipolysis, partly explained by reduced protein expression of ATGL and phosphorylated HSL. This effect was mimicked by ROCK inhibitor treatment, placing RND3 upstream of ROCK in the lipolysis regulatory pathway. siRNA knockdown in primary human adipocytes, lipolysis assays, ATGL/HSL western blotting, ROCK inhibitor phenocopy Metabolism: clinical and experimental Medium 31672447
2008 RhoE is required for keratinocyte differentiation and stratification. RhoE protein levels are specifically and transiently upregulated upon keratinocyte differentiation, and this upregulation requires ROCK I activity. RhoE overexpression caused cell enlargement and increased stratification; RhoE depletion induced hyperproliferation and delayed differentiation initiation. RhoE negatively modulates integrin adhesion in basal cells to facilitate detachment for suprabasal migration. siRNA depletion, adenoviral overexpression, 3D organotypic stratification model, BrdU proliferation assay, integrin adhesion assays, western blotting for differentiation markers Molecular biology of the cell Medium 18923151
2007 Mutant B-RAF (V600E) maintains Rnd3 expression via the MEK/ERK1/2 pathway in melanoma cells. B-RAF knockdown or MEK inhibition attenuated Rnd3 expression and elevated RhoA/ROCK/LIMK-2 signaling, increasing cofilin phosphorylation and stress fiber formation. Constitutive Rnd3 expression suppressed the actin and focal adhesion effects of B-RAF knockdown, placing Rnd3 as a cross-talk regulator between RAF/MEK/ERK and Rho/ROCK signaling pathways. siRNA knockdown of B-RAF, MEK pharmacological inhibition, constitutive Rnd3 expression rescue, cofilin/LIMK-2 phosphorylation western blotting, focal adhesion imaging Molecular biology of the cell Medium 18045987
2009 RhoE induces neurite-like outgrowth in PC12 cells in the absence of NGF, acting through inhibition of the RhoA/ROCK I signaling pathway. RhoE overexpression decreased RhoA activity and reduced ROCK I and phospho-MLCP expression. Overexpression of active RhoA or ROCK I abolished RhoE-promoted neurite outgrowth. RhoE siRNA knockdown reduced NGF-induced neurite formation, and Rac/Cdc42 also contribute to RhoE-induced neurite outgrowth. RhoE overexpression, dominant-active RhoA/ROCK I rescue, siRNA knockdown, RhoA activity assay, MLCP phosphorylation western blot, neurite measurement Journal of neurochemistry Medium 19968760
2024 KIAA1429 (m6A methyltransferase component) negatively regulates RND3 mRNA stability in coordination with the m6A reader YTHDC1. KIAA1429 mediates m6A modification of RND3 mRNA via its RNA binding domain. RNA stability assays, RIP, and MeRIP-qPCR established that increased m6A modification leads to decreased RND3 mRNA stability and expression. RNA stability assays, RNA immunoprecipitation (RIP), MeRIP-qPCR, luciferase assay, KIAA1429 and YTHDC1 knockdown/overexpression Cancer letters Medium 38224863

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 RhoE binds to ROCK I and inhibits downstream signaling. Molecular and cellular biology 244 12773565
2008 PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nature cell biology 217 18204440
1998 RhoE regulates actin cytoskeleton organization and cell migration. Molecular and cellular biology 190 9671486
2005 RhoE function is regulated by ROCK I-mediated phosphorylation. The EMBO journal 135 15775972
2017 The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3. Cell death & disease 102 29022920
2004 RhoE inhibits cell cycle progression and Ras-induced transformation. Molecular and cellular biology 99 15340047
2000 Induced expression of Rnd3 is associated with transformation of polarized epithelial cells by the Raf-MEK-extracellular signal-regulated kinase pathway. Molecular and cellular biology 93 11094087
2016 Chaperone-mediated autophagy regulates proliferation by targeting RND3 in gastric cancer. Autophagy 83 26761524
2000 A novel C3-like ADP-ribosyltransferase from Staphylococcus aureus modifying RhoE and Rnd3. The Journal of biological chemistry 79 11124969
2009 Rnd3 regulation of the actin cytoskeleton promotes melanoma migration and invasive outgrowth in three dimensions. Cancer research 77 19244113
2005 Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis. The Prostate 77 15754346
2006 RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress. Current biology : CB 76 17174923
2007 B-RAF regulation of Rnd3 participates in actin cytoskeletal and focal adhesion organization. Molecular biology of the cell 67 18045987
2013 A genome-wide screen of CREB occupancy identifies the RhoA inhibitors Par6C and Rnd3 as regulators of BDNF-induced synaptogenesis. PloS one 65 23762244
2012 Up-regulated miR-17 promotes cell proliferation, tumour growth and cell cycle progression by targeting the RND3 tumour suppressor gene in colorectal carcinoma. The Biochemical journal 61 22132820
2015 Pathophysiological Functions of Rnd3/RhoE. Comprehensive Physiology 60 26756630
2011 Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. Biochemical and biophysical research communications 58 22037464
2010 MicroRNA-200b regulates cyclin D1 expression and promotes S-phase entry by targeting RND3 in HeLa cells. Molecular and cellular biochemistry 58 20683643
2008 RhoE controls myoblast alignment prior fusion through RhoA and ROCK. Cell death and differentiation 58 18369372
2005 Function and regulation of RhoE. Biochemical Society transactions 58 16042565
2014 An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration. Nature communications 57 24572910
2006 RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line. Experimental cell research 55 17182035
2012 Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion. Hepatology (Baltimore, Md.) 54 22234932
2009 Regulation of Rnd3 localization and function by protein kinase C alpha-mediated phosphorylation. The Biochemical journal 51 19723022
2008 Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure. The EMBO journal 51 18946488
2016 Rnd3 in Cancer: A Review of the Evidence for Tumor Promoter or Suppressor. Molecular cancer research : MCR 50 27555595
2019 RhoE Fine-Tunes Inflammatory Response in Myocardial Infarction. Circulation 48 30586715
2016 A RhoA and Rnd3 cycle regulates actin reassembly during membrane blebbing. Proceedings of the National Academy of Sciences of the United States of America 48 26976596
2013 MicroRNA-200c regulates the sensitivity of chemotherapy of gastric cancer SGC7901/DDP cells by directly targeting RhoE. Pathology oncology research : POR 48 23821457
2013 Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling. Proceedings of the National Academy of Sciences of the United States of America 46 23630292
2013 RhoE is frequently down-regulated in hepatocellular carcinoma (HCC) and suppresses HCC invasion through antagonizing the Rho/Rho-kinase/myosin phosphatase target pathway. Hepatology (Baltimore, Md.) 44 22829315
2012 RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 44 22477709
2013 Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and -independent mechanisms. Nature communications 42 23535656
2021 RND3 attenuates oxidative stress and vascular remodeling in spontaneously hypertensive rat via inhibiting ROCK1 signaling. Redox biology 41 34883403
2010 Reduced expression of the ROCK inhibitor Rnd3 is associated with increased invasiveness and metastatic potential in mesenchymal tumor cells. PloS one 41 21209796
2018 Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE. Molecular therapy. Nucleic acids 40 30195759
2015 Mitomycin C induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b and its targeting of RhoE. European journal of pharmacology 40 26254780
2011 RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice. PloS one 40 21552537
2011 FOXD3 regulates migration properties and Rnd3 expression in melanoma cells. Molecular cancer research : MCR 39 21478267
2016 Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1α/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1α and Regulates Responsive Cardiac Angiogenesis. Hypertension (Dallas, Tex. : 1979) 38 26781283
2003 Modulation of RhoA-Rho kinase-mediated Ca2+ sensitization of rabbit myometrium during pregnancy - role of Rnd3. The Journal of physiology 37 14561824
2022 Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling. Theranostics 35 36438502
2020 Epstein-Barr Virus miRNA BART2-5p Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing RND3. Cancer research 35 32060148
2014 TGF-β1 stimulates human Tenon's capsule fibroblast proliferation by miR-200b and its targeting of p27/kip1 and RND3. Investigative ophthalmology & visual science 35 24667864
2013 Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts. Molecular biology of the cell 34 24284899
2012 Rnd1 and Rnd3 targeting to lipid raft is required for p190 RhoGAP activation. Molecular biology of the cell 34 22357615
2006 The protective role of a small GTPase RhoE against UVB-induced DNA damage in keratinocytes. The Journal of biological chemistry 34 17170105
2020 Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes. International journal of molecular medicine 33 32705255
2019 Overexpressed long noncoding RNA TUG1 affects the cell cycle, proliferation, and apoptosis of pancreatic cancer partly through suppressing RND3 and MT2A. OncoTargets and therapy 33 30787623
2016 RhoE/ROCK2 regulates chemoresistance through NF-κB/IL-6/ STAT3 signaling in hepatocellular carcinoma. Oncotarget 33 27213590
2008 RhoE Is required for keratinocyte differentiation and stratification. Molecular biology of the cell 33 18923151
2019 Copper promotes the migration of bone marrow mesenchymal stem cells via Rnd3-dependent cytoskeleton remodeling. Journal of cellular physiology 32 31187497
2016 The RhoE/ROCK/ARHGAP25 signaling pathway controls cell invasion by inhibition of Rac activity. Molecular biology of the cell 32 27413008
2016 RND3 promotes Snail 1 protein degradation and inhibits glioblastoma cell migration and invasion. Oncotarget 32 27705942
2014 Genetic deletion of Rnd3/RhoE results in mouse heart calcium leakage through upregulation of protein kinase A signaling. Circulation research 32 25348166
2014 Rnd3 haploinsufficient mice are predisposed to hemodynamic stress and develop apoptotic cardiomyopathy with heart failure. Cell death & disease 31 24901055
2016 microRNA-802/Rnd3 pathway imposes on carcinogenesis and metastasis of fine particulate matter exposure. Oncotarget 30 27144337
2015 miR-128 regulates the apoptosis and proliferation of glioma cells by targeting RhoE. Oncology letters 30 26870304
2018 Highly expressed miR-182-5p can promote preeclampsia progression by degrading RND3 and inhibiting HTR-8/SVneo cell invasion. European review for medical and pharmacological sciences 29 30402829
2016 Rnd3 as a Novel Target to Ameliorate Microvascular Leakage. Journal of the American Heart Association 29 27048969
2009 RhoE inhibits 4E-BP1 phosphorylation and eIF4E function impairing cap-dependent translation. The Journal of biological chemistry 29 19850923
2007 Overexpression of RhoE in Non-small Cell Lung Cancer (NSCLC) is associated with smoking and correlates with DNA copy number changes. Cancer biology & therapy 29 17312384
2023 Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6. Clinical and translational medicine 28 37743632
2014 Rnd3 regulates lung cancer cell proliferation through notch signaling. PloS one 28 25372032
2025 Rnd3 protects against doxorubicin-induced cardiotoxicity through inhibition of PANoptosis in a Rock1/Drp1/mitochondrial fission-dependent manner. Cell death & disease 27 39755713
2010 The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin-related domain. PloS one 27 20811643
2020 Upregulation of RND3 Affects Trophoblast Proliferation, Apoptosis, and Migration at the Maternal-Fetal Interface. Frontiers in cell and developmental biology 26 32232044
2008 RhoE enhances multidrug resistance of gastric cancer cells by suppressing Bax. Biochemical and biophysical research communications 26 19101510
2002 Crystal structure of the core domain of RhoE/Rnd3: a constitutively activated small G protein. Biochemistry 25 12009891
2024 KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells. Cancer letters 24 38224863
2018 miR-200b/c targets the expression of RhoE and inhibits the proliferation and invasion of non-small cell lung cancer cells. International journal of oncology 24 30066855
2015 Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity. Cancer medicine 24 26108681
2012 Neuronal polarization is impaired in mice lacking RhoE expression. Journal of neurochemistry 24 22428561
2007 RhoE participates in the stimulation of the inflammatory response induced by ethanol in astrocytes. Experimental cell research 24 17707794
2019 Long Non-Coding RNA HOXA-AS2 Enhances The Malignant Biological Behaviors In Glioma By Epigenetically Regulating RND3 Expression. OncoTargets and therapy 23 31819475
2018 A Rnd3/p190RhoGAP pathway regulates RhoA activity in idiopathic pulmonary fibrosis fibroblasts. Molecular biology of the cell 23 29995590
2011 A switch in RND3-RHOA signaling is critical for melanoma cell invasion following mutant-BRAF inhibition. Molecular cancer 23 21917148
2024 Berberine inhibits excessive autophagy and protects myocardium against ischemia/reperfusion injury via the RhoE/AMPK pathway. International journal of molecular medicine 22 38577949
2012 RhoE is regulated by cyclic AMP and promotes fusion of human BeWo choriocarcinoma cells. PloS one 22 22272352
2020 Inhibition of microRNA-128-3p alleviates liver ischaemia-reperfusion injury in mice through repressing the Rnd3/NF-κB axis. Innate immunity 21 32486927
2013 RhoE regulates actin cytoskeleton organization in human periodontal ligament cells under mechanical stress. Archives of oral biology 21 24370190
2014 The Rho GTPase RhoE is a p53-regulated candidate tumor suppressor in cancer cells. International journal of oncology 20 24399089
2005 Rnd3/RhoE induces tight junction formation in mammary epithelial tumor cells. Experimental cell research 20 15777789
2016 MicroRNA-200b inhibits epithelial-mesenchymal transition and migration of cervical cancer cells by directly targeting RhoE. Molecular medicine reports 19 26935796
2013 RhoE promotes metastasis in gastric cancer through a mechanism dependent on enhanced expression of CXCR4. PloS one 19 24312338
2012 Rnd3 induces stress fibres in endothelial cells through RhoB. Biology open 19 23430146
2008 N-terminus-mediated dimerization of ROCK-I is required for RhoE binding and actin reorganization. The Biochemical journal 19 18215121
2008 Staphylococcal enterotoxin B causes differential expression of Rnd3 and RhoA in renal proximal tubule epithelial cells while inducing actin stress fiber assembly and apoptosis. Microbial pathogenesis 19 18721871
2016 Rnd3-induced cell rounding requires interaction with Plexin-B2. Journal of cell science 18 27656111
2014 Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling. Cancer research 18 24525741
2009 RhoE stimulates neurite-like outgrowth in PC12 cells through inhibition of the RhoA/ROCK-I signalling. Journal of neurochemistry 18 19968760
2019 The Rho GTPase RND3 regulates adipocyte lipolysis. Metabolism: clinical and experimental 17 31672447
2015 Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer. PLoS genetics 17 26132659
2013 The Rho family member RhoE interacts with Skp2 and is degraded at the proteasome during cell cycle progression. The Journal of biological chemistry 17 24045951
2011 Epigenetic modification of RhoE expression in gastric cancer cells. Oncology reports 17 21109974
2019 Knockdown of RhoE Expression Enhances TGF-β-Induced EMT (epithelial-to-mesenchymal transition) in Cervical Cancer HeLa Cells. International journal of molecular sciences 16 31546735
2009 Xenopus Rnd1 and Rnd3 GTP-binding proteins are expressed under the control of segmentation clock and required for somite formation. Developmental dynamics : an official publication of the American Association of Anatomists 16 19795516
2021 Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 34046947
2015 RhoE is required for contact inhibition and negatively regulates tumor initiation and progression. Oncotarget 14 26036260
2006 Inhibition of ROCK by RhoE. Methods in enzymology 14 16472685

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