Affinage

RASD1

Dexamethasone-induced Ras-related protein 1 · UniProt Q9Y272

Length
281 aa
Mass
31.6 kDa
Annotated
2026-04-28
80 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RASD1 (Dexras1) is a dexamethasone-inducible Ras-family small GTPase that functions as a physiological effector of nitric oxide signaling, coupling NMDA receptor activation through the nNOS–CAPON–Dexras1 ternary complex to diverse downstream outputs including G-protein–dependent inhibition of adenylyl cyclase/CREB, ERK/MAPK modulation, and DMT1-mediated neuronal iron uptake (PMID:11086993, PMID:15020218, PMID:16908409). Activation occurs via S-nitrosylation at Cys11, which is antagonized by PKA-mediated phosphorylation at Ser253, establishing a biochemical switch that integrates NO and cAMP signaling (PMID:12498886, PMID:26358293). Through Gβγ- and Gαi-dependent signaling, RASD1 inhibits cAMP accumulation and CREB-driven transcription in neuroendocrine cells, modulates N-type calcium and TRPC4 channel activity, and regulates circadian photic entrainment in the suprachiasmatic nucleus (PMID:15020218, PMID:18815223, PMID:15339652). RASD1 additionally acts in the nucleus to suppress FE65–APP-mediated transcription and antagonize Ear2-mediated renin repression, and is required for glucocorticoid-driven adipogenesis, exercise-induced hippocampal neurogenesis, and oocyte meiotic progression (PMID:18922798, PMID:21247419, PMID:24297897, PMID:29593295, PMID:27997888).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Establishing that Dexras1 is a physiological NO target resolved how NMDA receptor signaling reaches the Ras superfamily: CAPON bridges nNOS to Dexras1, and NO selectively activates Dexras1 but not other Ras proteins in neurons and nNOS-knockout brains.

    Evidence Co-immunoprecipitation, GTPase activation assays with NO donors, NMDA stimulation in cortical neurons, nNOS-knockout mice

    PMID:11086993

    Open questions at the time
    • Structure of the ternary complex unresolved
    • Stoichiometry and affinity of CAPON–Dexras1 interaction not determined
    • Whether other NOS isoforms can substitute for nNOS in forming the complex was untested
  2. 2001 High

    Demonstrating that activated Dexras1 inhibits hormone secretion and receptor–Gi coupling to ERK revealed it as a prenylation-dependent modulator of G-protein signaling rather than a canonical Ras-like mitogenic activator.

    Evidence Constitutively active A178V mutant inhibited peptide secretion in AtT-20 cells (CAAX-dependent); Dexras1 impaired pertussis toxin–catalyzed ADP-ribosylation of Gαi and receptor-stimulated ERK in COS-7/HEK293 cells

    PMID:11356714 PMID:11751935

    Open questions at the time
    • Direct physical interaction with Gαi subunits not demonstrated at this stage
    • Whether prenylation targets Dexras1 to specific membrane microdomains unknown
  3. 2002 High

    Mapping the NO-responsive site to a single residue (Cys11) established S-nitrosylation as the precise post-translational mechanism activating Dexras1 GTPase cycling.

    Evidence Nitrosopeptide mapping and radiolabeling of S-nitrosylated cysteines with C11 mutagenesis abolishing NO-stimulated nucleotide exchange

    PMID:12498886

    Open questions at the time
    • Kinetics of S-nitrosylation/denitrosylation in living neurons not measured
    • Identity of denitrosylase enzymes for Dexras1 unknown
  4. 2004 High

    Dissecting the adenylyl cyclase inhibition pathway showed Dexras1 acts receptor-independently through Gβγ of PTX-sensitive G proteins to suppress cAMP and CREB, while knockout mice revealed Dexras1 as a gate for photic versus nonphotic circadian entrainment via ERK in the SCN.

    Evidence cAMP and CREB assays with PTX, RGS4, dominant-negative Gαi2 in cultured cells; Dexras1-KO mice with circadian behavioral assays and NMDA/NPY pharmacology

    PMID:15020218 PMID:15339652

    Open questions at the time
    • Precise mechanism by which a Ras-family GTPase activates heterotrimeric Gβγ remained unclear
    • Which adenylyl cyclase isoforms are the primary targets in SCN neurons not defined
  5. 2006 High

    Identifying PAP7–DMT1 as downstream effectors established that Dexras1 channels NO signaling into neuronal iron uptake, linking NMDA excitotoxicity to iron-dependent oxidative damage.

    Evidence Co-IP/pulldown of Dexras1–PAP7–DMT1, iron uptake assays, iron chelation blocking NMDA neurotoxicity in cortical cultures

    PMID:16908409

    Open questions at the time
    • Whether PAP7 directly couples to Dexras1 GTP-bound form or acts constitutively not resolved
    • Iron species and compartmental source initially unspecified
  6. 2008 High

    Extending Dexras1 function to transcription and ion channels: Dexras1 suppresses FE65–APP-mediated transcription (including GSK3β/Tau phosphorylation regulation) and triggers tonic Gβγ-dependent inhibition of N-type Ca²⁺ channels, actions unique among Ras proteins.

    Evidence Reciprocal Co-IP of Dexras1–FE65, siRNA knockdown increasing GSK3β and phospho-Tau; whole-cell patch clamp of CaV2.2 with PTX and Gβγ sequestration

    PMID:18815223 PMID:18922798

    Open questions at the time
    • In vivo relevance of Dexras1–FE65 interaction for Alzheimer pathology not tested
    • Whether Dexras1 modulates other voltage-gated channel families unknown
  7. 2011 High

    Identifying Ear2 and NonO as nuclear partners showed Dexras1 directly regulates gene-specific transcription: it relieves Ear2-mediated renin repression and modulates NonO coactivator function at CRE sites, extending Dexras1 from membrane signaling to nuclear gene regulation.

    Evidence Yeast two-hybrid, endogenous Co-IP from mouse brain, ChIP at CRE sites, reporter assays with Dexras1 missense mutations abolishing Ear2 binding

    PMID:21247419 PMID:21915321

    Open questions at the time
    • Genome-wide set of Dexras1 transcriptional targets not defined
    • How GTP hydrolysis requirement for NonO interaction relates to nuclear GTPase cycling unknown
  8. 2013 High

    Genetic confirmation that Dexras1 is required for NMDA/NO-mediated neurotoxicity (but not H₂O₂ or staurosporine) and for glucocorticoid-driven adipogenesis established pathway-specific physiological roles in vivo.

    Evidence Dexras1-KO cortical neurons and retinal ganglion cells resistant to NO-mediated death; KO MEFs and mice with reduced adipogenesis and diet-induced obesity

    PMID:23426685 PMID:24297897

    Open questions at the time
    • Downstream iron-dependent cell death effectors not fully characterized
    • Adipogenic signaling branch downstream of Dexras1 (ERK vs. cAMP) not disambiguated at this point
  9. 2015 High

    Discovery that PKA phosphorylation at Ser253 antagonizes S-nitrosylation at Cys11 revealed a reciprocal post-translational switch controlling Dexras1 activation, linking adiponectin/cAMP signaling to NO-iron pathway gating.

    Evidence In vitro kinase assay, S253 mutagenesis, dose-dependent suppression of S-nitrosylation and iron uptake

    PMID:26358293

    Open questions at the time
    • Whether Ser253 phosphorylation alters Dexras1 protein interactions or localization not tested
    • Phosphatase responsible for Ser253 dephosphorylation unknown
  10. 2016 High

    Multiple studies converged on tissue-specific Dexras1 effector mechanisms: Dexras1 translocates to the plasma membrane via its unique C-terminus to engage Shc–Raf–MAPK for adipogenesis, inhibits cAMP-CREB in vasopressin neurons in vivo, modulates glutamatergic excitability via lysosomal iron–PKC/Src/NR2A, and is required for oocyte MI-to-MII transition.

    Evidence Subcellular fractionation and Co-IP with Shc/Raf; in vivo lentiviral Rasd1 in rat SON; Dexras1-KO hippocampal slice electrophysiology; RNAi in mouse oocytes with spindle/chromosome phenotyping

    PMID:26739966 PMID:27080392 PMID:27345868 PMID:27997888

    Open questions at the time
    • Structural basis for C-terminal-dependent membrane translocation unresolved
    • Identity of the GEF activating Dexras1 downstream of insulin/IGF-1 unknown
    • Whether oocyte function involves NO-dependent or G-protein-dependent arm not determined
  11. 2018 High

    Extending circuitry in the brain, Dexras1 was shown to mediate exercise-induced hippocampal neurogenesis downstream of NMDA–ERK–CREB signaling, and the nNOS–CAPON–Dexras1 complex was placed downstream of NF-κB in anxiety-related hippocampal circuits.

    Evidence Dexras1-KO mice with exercise paradigm, BrdU labeling, NMDA pharmacology; chronic stress model with intra-hippocampal NF-κB inhibition and CAPON overexpression

    PMID:29593295 PMID:29858554

    Open questions at the time
    • Cell-type specificity of Dexras1 function in hippocampal neurogenesis not resolved
    • Whether NF-κB regulation of the ternary complex is transcriptional or post-translational not fully delineated
  12. 2019 High

    Demonstrating that Dexras1 deletion and iron chelation are both neuroprotective in autoimmune optic neuritis validated the NO–Dexras1–DMT1–iron axis as a therapeutic target in neuroinflammatory disease, with iNOS from microglia also capable of driving Dexras1 S-nitrosylation.

    Evidence Dexras1-KO mice in EAE model with deferiprone iron chelation, retinal ganglion cell and axon quantification

    PMID:31406150

    Open questions at the time
    • Whether Dexras1 contributes to iron-mediated injury in other demyelinating diseases untested
    • Relative contributions of iNOS vs. nNOS to Dexras1 activation in vivo not quantified
  13. 2022 Medium

    Extending Dexras1 pathology to white matter injury, Dexras1 was found to induce oligodendrocyte dysdifferentiation and myelin damage after subarachnoid hemorrhage through cAMP–CREB inhibition.

    Evidence Intracerebroventricular lentiviral Dexras1 gain- and loss-of-function, TEM, cAMP-CREB measurement in oxyhemoglobin-treated OPCs

    PMID:36230939

    Open questions at the time
    • Whether Dexras1 acts directly in OPCs or via neuronal iron release not disambiguated
    • Single-lab finding awaits independent replication
  14. 2025 High

    S-nitrosylated Dexras1 accumulates in peri-infarct cortex after ischemic stroke, and its inhibition (knockdown or dominant-negative C11S) promotes functional recovery by restoring neuronal excitability and dendritic spine density, establishing SNO-Dexras1 as a modifier of post-stroke plasticity.

    Evidence Photothrombotic stroke model with AAV-mediated Dexras1 knockdown or C11S overexpression, behavioral tests, electrophysiology, Golgi staining

    PMID:39749632

    Open questions at the time
    • Downstream mechanism linking SNO-Dexras1 to spine loss (iron vs. cAMP vs. ERK) not resolved
    • Therapeutic window for Dexras1 inhibition post-stroke not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for Dexras1's unique ability to activate heterotrimeric Gβγ, the identity of GEFs and GAPs regulating Dexras1 cycling in vivo, genome-wide transcriptional targets of nuclear Dexras1, and how iron-dependent and cAMP-dependent effector arms are differentially engaged across tissues.
  • No GEF or GAP for Dexras1 has been identified
  • Structural mechanism for Ras-to-heterotrimeric-G-protein coupling unknown
  • Relative contribution of individual effector arms (iron, cAMP, MAPK) in each tissue context not systematically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 11 R-HSA-112316 Neuronal System 6 R-HSA-382551 Transport of small molecules 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9909396 Circadian clock 2
Partners
ACSL4APBB1NONONOS1NOS1APNR2F6SHC1SLC11A2
Complex memberships
Dexras1-PAP7-DMT1 iron transport complexnNOS-CAPON-Dexras1 ternary complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 RASD1 (Dexras1) is specifically coupled to neuronal nitric oxide synthase (nNOS) via the adaptor protein CAPON, forming a ternary nNOS-CAPON-Dexras1 complex. This complex enhances NO-mediated activation of Dexras1, which is activated by NO donors and by NMDA receptor-stimulated NO synthesis in cortical neurons. Selective decrease of Dexras1 activation (but not H-Ras or four other Ras family members) was observed in nNOS-/- mouse brains, identifying Dexras1 as a physiologic NO effector. Co-immunoprecipitation, GTPase activation assays with NO donors, NMDA receptor stimulation in cortical neurons, nNOS knockout mice Neuron High 11086993
2002 S-nitrosylation of Dexras1 occurs on a single cysteine residue, Cys11. Mutagenesis of Cys11 abolished the effect of NO donors on Dexras1 guanine nucleotide exchange activity, identifying this residue as the critical site for NO-mediated activation. Nitrosopeptide mapping (2D peptide chromatography), radiolabeling of S-nitrosylated cysteines, site-directed mutagenesis Chemistry & Biology High 12498886
2001 Constitutively active Dexras1[A178V] inhibits cAMP-stimulated peptide hormone secretion in AtT-20 corticotroph cells by 86%. This inhibition requires prenylation, as a CAAX-box deletion mutant (Dexras1[A178V/C277term]) did not inhibit secretion. Wild-type Dexras1 had no effect, indicating activation state dependency. Transient transfection of wild-type and constitutively active mutant Dexras1 with hGH secretion assay, GTP/GDP ratio measurement Endocrinology High 11356714
2001 Dexras1 inhibits ligand-dependent signal transduction from the Gi-coupled formyl peptide receptor (FPR) to ERK-1/2 MAPK. Dexras1 expression impaired pertussis toxin-catalyzed ADP-ribosylation of membrane-associated Gi-alpha and decreased GTPgammaS binding in f-MLF-stimulated membranes, indicating Dexras1 acts very proximally at receptor-Gi coupling. While Dexras1 alone weakly activates ERK, it inhibits ligand-stimulated ERK activation. Transient co-transfection in COS-7 and HEK-293 cells, immune complex in vitro kinase assay (HA-Erk-2), pertussis toxin treatment, ADP-ribosylation assay, GTPgammaS binding Journal of Biological Chemistry High 11751935
2004 Dexras1 inhibits adenylyl cyclase activity by activating both the Gi-alpha and Gbetagamma arms of the Gi signaling cascade in a receptor-independent manner. This inhibition is blocked by pertussis toxin or RGS4 co-expression but not by dominant-interfering Gi-alpha2 mutants, indicating Gbetagamma dependence. Dexras1 also decreases forskolin-stimulated CREB activation. cAMP measurement, pertussis toxin treatment, RGS4 co-expression, dominant-negative Gi-alpha2 mutants, CREB activation assays Biochemical and Biophysical Research Communications High 15020218
2004 Dexras1 potentiates photic entrainment and suppresses nonphotic responses of the circadian clock. Mechanistically, Dexras1 couples NMDA receptor and light input to Gi/o and ERK activation in the suprachiasmatic nucleus (SCN). Dexras1 knockout eliminates a pertussis-sensitive circadian response to NMDA and greatly potentiates nonphotic responses to neuropeptide Y. Dexras1 knockout mice, circadian behavioral assays, pharmacological pertussis toxin treatment, ERK activation measurement, NMDA/neuropeptide Y challenge Neuron High 15339652
2004 AGS1/RASD1 suppresses cell growth and induces apoptosis. In NIH-3T3, MCF-7, and A549 cells, RASD1 markedly diminished clonogenic colony number. Adenoviral RASD1 expression inhibited log-phase growth and increased apoptosis in vitro, and inhibited subcutaneous tumor growth of A549 cells in athymic nude mice in vivo. Clonogenic assay, adenoviral overexpression, in vitro growth assay, apoptosis measurement, in vivo xenograft model Oncogene High 15184869
2005 Dexras1 blocks receptor-mediated heterologous sensitization of adenylyl cyclase 1 (AC1). Dexras1 does not alter acute D2L receptor-mediated inhibition of AC1, but completely blocks D2L receptor-induced heterologous sensitization of AC1. This effect requires Dexras1 nucleotide binding (a G31V nucleotide-binding-deficient mutant had no effect) and is Gbetagamma-dependent. HEK293 cell transfection, cAMP assay, ERK1/2 phosphorylation, nucleotide-binding-deficient mutant (G31V), betaARK-ct Gbetagamma sequestration Biochemical and Biophysical Research Communications High 15913563
2006 RASD1 (Dexras1) binds to PAP7 (peripheral benzodiazepine receptor-associated protein), which in turn binds to DMT1 (divalent metal transporter 1), an iron import channel. NMDA receptor activation leads to nNOS activation, S-nitrosylation and activation of Dexras1, which via PAP7 and DMT1 physiologically induces iron uptake in neurons. Selective iron chelation prevents NMDA neurotoxicity, implicating this cascade in NMDA excitotoxicity. Co-immunoprecipitation, pulldown assays, iron uptake assays, iron chelation, NMDA neurotoxicity in cortical cultures Neuron High 16908409
2006 Dexras1 shapes the photic responsiveness of the mammalian circadian clock by repressing PACAP/PAC1-ERK/MAPK signaling during the late night and limiting ERK/MAPK activation during the early night (NMDA-mediated pathway). Dexras1-deficient mice exhibit a restructured nighttime phase response curve and loss of gating to photic resetting during the day. During the daytime, Dexras1 mediates a novel pathway stimulating ERK/MAPK in the SCN shell to trigger clock protein downregulation. Dexras1 knockout mice, phase response curve analysis, ERK/MAPK immunostaining, PACAP/NMDA pharmacology Journal of Neuroscience High 17167088
2003 A glucocorticoid response element (GRE) located 2.3 kb downstream of the poly(A) signal in the 3'-flanking region of the human RASD1 gene mediates rapid glucocorticoid responsiveness. A point mutation within the 15-bp GRE abolished glucocorticoid-induced transcription. Reporter gene assay (luciferase), GRE mutagenesis Biochimica et Biophysica Acta Medium 12818426
2008 Dexras1 binds to the PTB2 domain of FE65 (an APP adaptor protein) and potently suppresses FE65-APP-mediated transcription (including GSK3beta). Dexras1 and APP can simultaneously bind FE65 PTB2, so suppression is not due to competition for FE65. Phosphorylation of FE65 tyrosine 547 reduces binding of Dexras1 to FE65 and thereby enhances FE65-APP transcription. siRNA knockdown of Dexras1 enhances GSK3beta expression and increases Tau phosphorylation. Co-immunoprecipitation, pulldown, reporter gene assay, siRNA knockdown, western blotting for phospho-Tau Journal of Biological Chemistry High 18922798
2008 AGS1/Dexras1 triggers tonic Gbetagamma signaling and selectively attenuates receptor-initiated signaling by Gbetagamma subunits of PTX-sensitive G proteins (Gi), thereby reducing basal current density and causing voltage-dependent inhibition of N-type Ca2+ channels (CaV2.2). These effects are blocked by pertussis toxin or a Gbetagamma-sequestering peptide (masGRK3ct). No other tested Ras proteins duplicated this effect. Whole-cell patch clamp in HEK293 cells expressing CaV2.2, pertussis toxin treatment, Gbetagamma sequestration peptide, comparison with panel of other Ras proteins American Journal of Physiology - Cell Physiology High 18815223
2011 Rasd1 interacts with Ear2 (Nr2f6, a negative regulator of renin transcription) via Ear2's ligand binding domain, and this interaction inhibits Ear2-mediated repression of renin transcription. shRNA-mediated knockdown of Rasd1 results in further repression of renin transcription, while Rasd1 overexpression upregulates endogenous renin mRNA. Rasd1 missense mutations that attenuate physical interaction with Ear2 also abolish the functional counteraction of Ear2-mediated repression. Yeast two-hybrid, in vitro binding assay, Co-IP in COS-7 and HEK293T cells, endogenous co-IP from mouse brain, luciferase reporter assay, shRNA knockdown, real-time RT-PCR BMC Molecular Biology High 21247419
2011 Rasd1 interacts with NonO (p54nrb), a multifunctional protein involved in cAMP pathway transcriptional activation. This interaction requires GTP hydrolysis activity of Rasd1. Rasd1 and NonO interact at CRE-sites of specific target genes and Rasd1 modulates the coactivator function of NonO in the cAMP pathway. Affinity pulldown, co-immunoprecipitation, indirect immunofluorescence, reporter gene assays, chromatin immunoprecipitation, gene knockdown PLoS One High 21915321
2011 AGS1/Dexras1 reduces cAMP accumulation in both vehicle-treated and agonist-treated cells (in contrast to Rhes which only affects agonist-stimulated cAMP), resulting in altered D1 receptor signal-to-noise ratio. Effects of AGS1/Dexras1 on cAMP were not blocked by pertussis toxin, suggesting interaction with a Galphai monomer. Both Rhes and AGS1/Dexras1 were found associated with GTP-bound Galphai in pulldown assays. cAMP accumulation assay in heterologous expression system, pertussis toxin treatment, GTP-agarose pulldown Journal of Neuroscience Research Medium 21374700
2012 Glucocorticoid receptor (GR) and STAT5b cooperatively mediate glucocorticoid-induced Rasd1 expression in pancreatic islets. Prolactin inhibits GR/STAT5b transcriptional activity on the Rasd1 gene. Knockdown of Rasd1 abolishes the inhibitory effects of dexamethasone on insulin secretion and the PKA, PKC, and ERK1/2 pathways in insulin-secreting cells. Chromatin immunoprecipitation (ChIP), siRNA knockdown, immunofluorescence, insulin secretion assays, kinase pathway analysis Endocrinology High 22700767
2013 Dexras1 is required for glutamate/NMDA neurotoxicity via NO-mediated iron influx. Iron influx is elicited by nitric oxide but not by other proapoptotic stimuli (H2O2, staurosporine). Deletion of Dexras1 in mice attenuates NO-mediated cell death in primary cortical neurons and retinal ganglion cells in vivo, demonstrating Dexras1 specifically mediates NMDA-elicited neurotoxicity through the NO-iron influx pathway. Dexras1 knockout mice, primary cortical neuron culture, in vivo retinal ganglion cell assay, NO donor vs. other apoptotic stimuli comparison Journal of Neuroscience High 23426685
2013 Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity. Adipogenic differentiation of 3T3-L1 cells is abolished by Dexras1 depletion and elicited by Dexras1 overexpression. Adipogenesis is markedly reduced in mouse embryonic fibroblasts from Dexras1-deleted mice, and adiposity and diet-induced weight gain are diminished in Dexras1 knockout mice. siRNA depletion, overexpression in 3T3-L1, Dexras1 knockout mouse embryonic fibroblasts, mouse diet-induced obesity model PNAS High 24297897
2014 Rasd1 selectively activates TRPC4 channels among all Ras proteins tested, requiring functional Galphai1 and Galphai3. Dexamethasone increases Rasd1 protein expression in INS-1 cells and thereby triggers a TRPC4-like cationic current. Electrophysiology (whole-cell patch clamp), transfection with panel of Ras proteins, co-expression with Galphai mutants, Rasd1 overexpression in INS-1 cells Pflugers Archiv Medium 25502319
2015 Dexras1 is phosphorylated by PKA on serine 253, which suppresses iron influx by reducing S-nitrosylation of Dexras1 in a dose-dependent manner. Adiponectin modulates Dexras1 via PKA, demonstrating functional crosstalk between S-nitrosylation and phosphorylation on Dexras1. In vitro kinase assay, site-directed mutagenesis (Ser253), S-nitrosylation measurement, iron uptake assay, PKA activators/inhibitors FEBS Letters High 26358293
2016 Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, requiring its unique C-terminal domain (amino acids 223-276). Dexras1-dependent MAPK activation is selectively involved in IGF-1 signaling. Dexras1 interacts with Shc and Raf, indicating that its activation of MAPK depends on the Shc-Grb2-Raf complex. Without Dexras1, MAPK activation and C/EBPbeta phosphorylation are abolished, blocking mitotic clonal expansion and adipocyte differentiation. Subcellular fractionation/localization, C-terminal domain deletion constructs, Co-IP of Dexras1 with Shc and Raf, MAPK/ERK phosphorylation assays, Dexras1 knockout cells Scientific Reports High 27345868
2016 RASD1 is required for MI-to-MII oocyte transition. Knockdown of Rasd1 arrests GV oocytes at MI stage with disrupted meiotic spindle formation and chromosomal misalignment. Rasd1 knockdown also misregulates Obox4 and Arp2/3, genes engaged in MI-MII transition and cytokinesis. RNAi microinjection into mouse oocytes, time-lapse video microscopy, immunofluorescence for spindle/chromosome alignment, qRT-PCR Cellular Physiology and Biochemistry Medium 27997888
2016 Rasd1 inhibits cAMP-PKA-CREB signaling in vasopressin neurons. Overexpression of Rasd1 mimics dexamethasone's decrease of forskolin-stimulated c-Fos, Nr4a1, and phosphorylated CREB expression; Rasd1 knockdown inhibits these effects. Inhibition requires isoprenylation (farnesyltransferase inhibitor FTI-277 and CAAX box deletion prevented Rasd1 inhibitory effects). Lentiviral Rasd1 overexpression in rat supraoptic nucleus (SON) in vivo diminished cAMP-inducible gene expression in response to osmotic stress. AtT20 cell overexpression and knockdown (dexamethasone mimicry), farnesyltransferase inhibitor, CAAX deletion mutant, lentiviral in vivo injection in rat SON, cAMP-stimulated gene expression analysis Molecular Brain High 26739966
2016 Lysosomal iron serves as the main source of intracellular iron signaling modulating glutamatergic excitability via Dexras1/DMT1. Genetic and pharmacological ablation of the Dexras1-DMT1 neuronal iron pathway increased glutamatergic transmission via synaptic modification of NMDA receptor activity through the PKC/Src/NR2A pathway, as shown by voltage-sensitive dye imaging and whole-cell patch clamping of hippocampal slices. Dexras1 knockout mice, pharmacological iron pathway ablation, voltage-sensitive dye imaging, whole-cell patch clamp, hippocampal slice electrophysiology Molecular Brain High 27080392
2017 Overexpression of RASD1 inhibits glioma cell migration and invasion and inactivates the AKT/mTOR signaling pathway, as shown by decreased phosphorylation of AKT and S6 ribosomal protein. In an intracranial xenograft model, RASD1 overexpression reduced tumor cell invasion without affecting tumor size. Lentivirus-mediated RASD1 overexpression, migration/invasion assays, intracellular signaling array (phospho-AKT, phospho-S6), intracranial xenograft model Scientific Reports Medium 28600528
2017 Rapid RASD1 expression in mouse uterine endometrium is regulated by estrogen receptor-dependent intracellular signaling including both p38-MAPK and ERK pathways. Estradiol (but not progesterone) rapidly induces Rasd1 within 2 hours; this induction is blocked by the ER antagonist ICI 182,780. Ovariectomized mouse model, estradiol/progesterone treatment, ER antagonist (ICI 182,780) pretreatment, western blot, RT-PCR, p38/ERK pathway inhibitors Molecular and Cellular Endocrinology Medium 28188843
2018 Hippocampal NF-κB mediates anxiogenic behaviors via regulation of the nNOS-CAPON-Dexras1 ternary complex. NF-κB inhibition by PDTC reversed CMS-induced upregulation of nNOS, CAPON, and Dexras1. Overexpression of CAPON in hippocampus induced nNOS-Dexras1 interaction and anxiety-like behaviors, and NF-κB inhibition reduced the CAPON-induced nNOS-Dexras1 complex and anxiogenic effects. Chronic mild stress mouse model, intra-hippocampal PDTC infusion, LV-CAPON overexpression, behavioral tests (NSF, EPM), Co-IP of nNOS-Dexras1 complex, western blot, immunohistochemistry Journal of Neurochemistry Medium 29858554
2018 Dexras1 is required for exercise-induced proliferation of neural progenitors in the hippocampal dentate gyrus. Dexras1 knockout abolishes exercise-dependent activation of ERK/MAPK and CREB, and inhibits upregulation of NMDA receptor subunit NR2A, bdnf, trkB, and vegf-a. NMDA receptor inhibition enhances SGZ cell proliferation in wild-type but not dexras1-deficient mice, placing Dexras1 downstream of NMDA receptor signaling in exercise-induced neurogenesis. Dexras1 knockout mice, exercise paradigm, BrdU/EdU labeling for proliferation, NMDA receptor pharmacology, ERK/MAPK and CREB phosphorylation assays, qPCR for neurogenic genes Scientific Reports High 29593295
2019 Dexras1 deletion and iron chelation with deferiprone are neuroprotective in experimental autoimmune encephalomyelitis (EAE) optic neuritis. Dexras1 is activated by S-nitrosylation by NO from inducible NOS (in microglia/macrophages) or nNOS (in neurons), and drives iron entry via DMT1, contributing to oxidative stress and neurodegeneration. Dexras1 knockout mice, EAE model, iron chelator (deferiprone) treatment, retinal ganglion cell and axon counts, visual function assessment Scientific Reports High 31406150
2022 Dexras1 induces oligodendrocyte dysdifferentiation and myelin injury after subarachnoid hemorrhage by inhibiting the cAMP-CREB pathway. Dexras1 overexpression significantly worsened OPC dysdifferentiation and myelin injury while knockdown ameliorated these changes. Mechanistically, Dexras1 overexpression inhibited the cAMP-CREB pathway in an in vitro SAH model. Intracerebroventricular lentiviral Dexras1 modulation (KD and OE), immunofluorescence, TEM, western blotting, primary neuron oxyhemoglobin treatment, cAMP-CREB pathway measurement Cells Medium 36230939
2024 KIAA1429 increases the m6A modification level of RASD1 mRNA and destabilizes it in an m6A-YTHDF2-dependent manner, thereby downregulating RASD1 expression and promoting gastric cancer progression. RASD1 knockdown partially rescued the anti-oncogenic effects of KIAA1429 knockdown. MeRIP-seq, MeRIP-qPCR, RNA stability assay, RIP assay, RNA pulldown, dual luciferase reporter, gain/loss-of-function in vitro and in vivo Journal of Translational Medicine High 38902717
2025 S-nitrosylation of Dexras1 (SNO-Dexras1) is elevated in the peri-infarct cortex after ischemic stroke (days 4-10), and inhibiting SNO-Dexras1 (by Dexras1 knockdown or dominant-negative C11S mutant) promotes motor functional recovery, enhances neuronal excitability (increased spike number and mEPSC frequency), and increases dendritic spine density in the peri-infarct cortex. Overexpression of Dexras1 worsens stroke outcome. Photothrombotic stroke model, AAV-mediated Dexras1 knockdown or Dexras1-C11S overexpression, behavioral tests (grid-walking, cylinder), western blot, Golgi staining, electrophysiology CNS Neuroscience & Therapeutics High 39749632

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nature genetics 738 16845398
2000 Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 269 11086993
2006 NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Neuron 222 16908409
2004 The Ras-related protein AGS1/RASD1 suppresses cell growth. Oncogene 93 15184869
2004 Dexras1 potentiates photic and suppresses nonphotic responses of the circadian clock. Neuron 92 15339652
1999 Rhes: A striatal-specific Ras homolog related to Dexras1. Journal of neuroscience research 82 10467249
2012 Fission yeast Ags1 confers the essential septum strength needed for safe gradual cell abscission. The Journal of cell biology 77 22891259
2001 Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases. The Journal of biological chemistry 66 11751935
2000 Aicardi-Goutières syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21. American journal of human genetics 64 10827106
2009 Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research 61 19549772
2013 Dexras1, a small GTPase, is required for glutamate-NMDA neurotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 23426685
2014 Downregulated RASD1 and upregulated miR-375 are involved in protective effects of calycosin on cerebral ischemia/reperfusion rats. Journal of the neurological sciences 57 24548484
2001 Dexras1/AGS-1, a steroid hormone-induced guanosine triphosphate-binding protein, inhibits 3',5'-cyclic adenosine monophosphate-stimulated secretion in AtT-20 corticotroph cells. Endocrinology 57 11356714
2002 Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on a single cysteine residue. Chemistry & biology 56 12498886
2006 The molecular gatekeeper Dexras1 sculpts the photic responsiveness of the mammalian circadian clock. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 17167088
2013 Calycosin induces apoptosis by upregulation of RASD1 in human breast cancer cells MCF-7. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 47 23609007
2008 Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription. The Journal of biological chemistry 43 18922798
2004 Dexras1 inhibits adenylyl cyclase. Biochemical and biophysical research communications 39 15020218
2005 Dexras1 blocks receptor-mediated heterologous sensitization of adenylyl cyclase 1. Biochemical and biophysical research communications 37 15913563
2013 Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity. Proceedings of the National Academy of Sciences of the United States of America 36 24297897
2016 Lysosomal iron modulates NMDA receptor-mediated excitation via small GTPase, Dexras1. Molecular brain 34 27080392
2016 Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation. Molecular brain 33 26739966
2011 Rhes and AGS1/Dexras1 affect signaling by dopamine D1 receptors through adenylyl cyclase. Journal of neuroscience research 33 21374700
2019 Tigliane Diterpenoids as a New Type of Antiadipogenic Agents Inhibit GRα-Dexras1 Axis in Adipocytes. Journal of medicinal chemistry 32 30707022
2018 Hippocampal nuclear factor kappa B accounts for stress-induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS-Dexras1 coupling. Journal of neurochemistry 32 29858554
2017 Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway. Scientific reports 30 28600528
2014 Up-regulating of RASD1 and apoptosis of DU-145 human prostate cancer cells induced by formononetin in vitro. Asian Pacific journal of cancer prevention : APJCP 29 24761910
2012 The regulation of Rasd1 expression by glucocorticoids and prolactin controls peripartum maternal insulin secretion. Endocrinology 27 22700767
2008 The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels. American journal of physiology. Cell physiology 27 18815223
2001 Regulation of Dexras1 expression by endogenous steroids. Neuroendocrinology 27 11598380
2018 Differential ability of formononetin to stimulate proliferation of endothelial cells and breast cancer cells via a feedback loop involving MicroRNA-375, RASD1, and ERα. Molecular carcinogenesis 25 29722068
2019 Dexras1 Deletion and Iron Chelation Promote Neuroprotection in Experimental Optic Neuritis. Scientific reports 22 31406150
2007 Changes in mRNA for CAPON and Dexras1 in adult rat following sciatic nerve transection. Journal of chemical neuroanatomy 22 17768032
2024 KIAA1429 promotes gastric cancer progression by destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. Journal of translational medicine 20 38902717
2016 Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis. Scientific reports 20 27345868
2003 Identification of a glucocorticoid response element in the 3'-flanking region of the human Dexras1 gene. Biochimica et biophysica acta 20 12818426
2011 Light-induced retinal ganglion cell damage in vivo involves Dexras1. Molecular vision 19 21245950
2006 Dexras1: shaping the responsiveness of the circadian clock. Seminars in cell & developmental biology 19 16765612
2017 MiR-301b-3p/3584-5p enhances low-dose mono-n-butyl phthalate (MBP)-induced proliferation by targeting Rasd1 in Sertoli cells. Toxicology in vitro : an international journal published in association with BIBRA 17 29162477
2023 Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage. CNS neuroscience & therapeutics 16 37735980
2017 Rapid expression of RASD1 is regulated by estrogen receptor-dependent intracellular signaling pathway in the mouse uterus. Molecular and cellular endocrinology 16 28188843
2018 Dexras1 is a homeostatic regulator of exercise-dependent proliferation and cell survival in the hippocampal neurogenic niche. Scientific reports 15 29593295
2014 Small G Proteins Dexras1 and RHES and Their Role in Pathophysiological Processes. International journal of cell biology 15 24817889
2014 Neurospora crassa 1,3-α-glucan synthase, AGS-1, is required for cell wall biosynthesis during macroconidia development. Microbiology (Reading, England) 15 24847001
2011 Rasd1 interacts with Ear2 (Nr2f6) to regulate renin transcription. BMC molecular biology 15 21247419
2015 PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation. FEBS letters 13 26358293
2020 Hsa-miR-375/RASD1 Signaling May Predict Local Control in Early Breast Cancer. Genes 12 33255991
2016 RASD1 Knockdown Results in Failure of Oocyte Maturation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 12 27997888
2011 Loss of dexras1 alters nonphotic circadian phase shifts and reveals a role for the intergeniculate leaflet (IGL) in gene-targeted mice. Chronobiology international 12 21834641
2011 Rasd1 modulates the coactivator function of NonO in the cyclic AMP pathway. PloS one 12 21915321
2008 Spatiotemporal expression of Dexras1 after spinal cord transection in rats. Cellular and molecular neurobiology 12 18219571
2016 Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating. Neuroscience 11 26946266
2017 Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma. Cold Spring Harbor molecular case studies 9 28487882
2014 Dexamethasone activates transient receptor potential canonical 4 (TRPC4) channels via Rasd1 small GTPase pathway. Pflugers Archiv : European journal of physiology 8 25502319
2012 Scheduled feeding alters the timing of the suprachiasmatic nucleus circadian clock in dexras1-deficient mice. Chronobiology international 8 22928915
2021 miR-375 acts as a novel factor modulating pituitary prolactin synthesis through Rasd1 and Esr1. The Journal of endocrinology 7 34014836
2022 Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage. Cells 6 36230939
2021 A nomogram for predicting metabolic steatohepatitis: The combination of NAMPT, RALGDS, GADD45B, FOSL2, RTP3, and RASD1. Open medicine (Warsaw, Poland) 6 34041361
2015 The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels. Channels (Austin, Tex.) 6 26083271
2007 Dex-ras1 and serum- and glucocorticoid-inducible protein kinase 1: regulation of expression by dexamethasone in HEK293 cells. Neurochemical research 6 17985234
2025 S-Nitrosylation of Dexras1 Controls Post-Stroke Recovery via Regulation of Neuronal Excitability and Dendritic Remodeling. CNS neuroscience & therapeutics 5 39749632
2022 Development and Application of a New Arabinose-Inducible Vector in High-Attachment Strain Stenotrophomonas AGS-1 from Aerobic Granular Sludge. ACS synthetic biology 5 34989221
2021 Expression of Rasd1 in mouse endocrine pituitary cells and its response to dexamethasone. Stress (Amsterdam, Netherlands) 5 33840368
2017 Rasd1 is an estrogen-responsive immediate early gene and modulates expression of late genes in rat anterior pituitary cells. Endocrine journal 5 28835591
2016 Circadian Dexras1 in rats: Development, location and responsiveness to light. Chronobiology international 5 26785766
2021 Sevoflurane protects against ischemia-reperfusion injury in mice after total knee arthroplasty via facilitating RASD1-mediated protein kinase A pathway activation. Aging 4 33982674
2004 Resetting the clock: Dexras1 defines a path. Neuron 4 15339641
2024 Knockdown of RASD1 improves MASLD progression by inhibiting the PI3K/AKT/mTOR pathway. Lipids in health and disease 3 39731125
2022 Ketamine alleviating depressive-like behaviors is associated with regulation of nNOS-CAPON-Dexras1 complex in chronic unpredictable mild stress rats. Translational neuroscience 3 36212606
2017 The role of Arabidopsis thaliana RASD1 gene in ABA-dependent abiotic stress response. Plant biology (Stuttgart, Germany) 3 29125669
2022 Genetic Analysis of RASD1 as a Candidate Gene for Schizophrenia. Balkan medical journal 2 36305088
2024 Long non-coding RNA SIX1-1 promotes proliferation of cervical cancer cells via negative transcriptional regulation of RASD1. Human cell 1 39014290
2023 Construction and application of a new CRISPR/Cas12a system in Stenotrophomonas AGS-1 from aerobic granular sludge. Biotechnology journal 1 37288647
2023 Construction of a CRISPR Interference System for Gene Knockdown in Stenotrophomonas maltophilia AGS-1 from Aerobic Granular Sludge. ACS synthetic biology 1 37906167
2026 Hypermethylation-mediated silencing of RASD1 drives multiple myeloma pathogenesis. Blood research 0 41627676
2026 S-nitrosylation of Dexras1 attenuates fear memory generalization in the infralimbic cortex. Brain research 0 41698630
2026 Dexras1 plays a crucial role in glucocorticoid-induced osteonecrosis of the femoral head by mediating imbalance between osteogenesis and adipogenesis. Cellular and molecular life sciences : CMLS 0 41807756
2025 HHQG ameliorates acute liver injury (ALI) by inhibiting NLRP3 activation through RASD1-mediated regulation of the PKCδ-NF-κB signaling pathway. Scientific reports 0 41254156
2024 Correction: Xin et al. Dexras1 Induces Dysdifferentiation of Oligodendrocytes and Myelin Injury by Inhibiting the cAMP-CREB Pathway after Subarachnoid Hemorrhage. Cells 2022, 11, 2976. Cells 0 39682783
2023 Construction and application of a mCherry fluorescent labeling system for Stenotrophomonas AGS-1 from aerobic granular sludge. FEMS microbiology letters 0 37567763