Affinage

RASD1

Dexamethasone-induced Ras-related protein 1 · UniProt Q9Y272

Length
281 aa
Mass
31.6 kDa
Annotated
2026-06-10
70 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RASD1/Dexras1 is a glucocorticoid-inducible, brain-enriched Ras-family small GTPase that transduces nitric oxide and hormonal signals into control of Gi/o-coupled signaling, neuronal iron handling, and circadian and metabolic physiology (PMID:11086993, PMID:15339652, PMID:24297897). It is activated post-translationally by S-nitrosylation on Cys11, a modification generated by nNOS and amplified within an nNOS–CAPON–Dexras1 ternary complex downstream of NMDA receptor activation (PMID:11086993, PMID:12498886). Activated Dexras1 recruits PAP7, which bridges to the divalent metal transporter DMT1 to drive NO-dependent neuronal iron uptake; this iron-influx pathway mediates NMDA excitotoxic and oxidative neuronal death and modulates synaptic NMDA receptor activity, and is opposed by PKA phosphorylation on Ser253, which suppresses S-nitrosylation (PMID:16908409, PMID:23426685, PMID:26358293, PMID:27080392, PMID:31406150). In the suprachiasmatic nucleus Dexras1 couples NMDA and photic input to Gi/o and ERK/MAPK signaling, shaping photic versus nonphotic circadian entrainment and time-of-day-specific clock responses (PMID:15339652, PMID:17167088). As a negative regulator of cAMP signaling it acts proximally at receptor–Gi coupling and adenylyl cyclase, inhibiting cAMP/PKA/CREB-driven gene expression and hormone secretion in a prenylation-dependent manner (PMID:11751935, PMID:15020218, PMID:26739966), and it uniquely activates TRPC4 channels through Gαi (PMID:25502319). Dexras1 also links glucocorticoid and IGF-1 signals to MAPK-driven adipogenesis via C-terminal membrane translocation and interaction with Shc and Raf (PMID:24297897, PMID:27345868), and engages transcriptional regulators including FE65, Ear2/Nr2f6, and NonO to modulate APP, renin, and CRE-dependent gene programs (PMID:18922798, PMID:21247419, PMID:21915321). RASD1 expression is itself controlled by glucocorticoid receptor/STAT5b transcription and by post-transcriptional and epigenetic silencing in cancer through m6A-YTHDF2-mediated mRNA degradation and DNMT1-dependent promoter methylation (PMID:22700767, PMID:38902717, PMID:39014290).

Mechanistic history

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

    Established Dexras1 as a physiologic effector of nitric oxide by placing it in a signaling complex with nNOS, answering how this GTPase is activated in neurons.

    Evidence Co-IP of an nNOS–CAPON–Dexras1 ternary complex with GTPase activation assays and nNOS-/- mice in cortical neurons

    PMID:11086993

    Open questions at the time
    • Did not define the chemical site of NO modification
    • Downstream effectors of activated Dexras1 not yet identified
  2. 2002 High

    Mapped NO activation to a single residue, defining Cys11 S-nitrosylation as the molecular switch for nucleotide exchange.

    Evidence Nitrosopeptide mapping and Cys11 site-directed mutagenesis in vitro

    PMID:12498886

    Open questions at the time
    • Structural basis of how nitrosylation drives exchange not resolved
    • In vivo contribution of Cys11 to phenotypes addressed only later
  3. 2001 High

    Defined Dexras1 as a negative regulator of cAMP and Gi-coupled receptor signaling acting at the receptor–Gi interface, with prenylation required for function.

    Evidence Co-transfection with FPR and a cAMP-secretion reporter, GTPγS binding, ADP-ribosylation, and CAAX-deletion mutants in COS-7/HEK293/AtT-20 cells

    PMID:11356714 PMID:11751935

    Open questions at the time
    • Mechanism of action at Gi not structurally defined
    • Endogenous receptor contexts not established
  4. 2003 Medium

    Identified an unusual 3'-flanking GRE controlling glucocorticoid-induced Dexras1 transcription, explaining its hormonal inducibility.

    Evidence Luciferase reporter with the 3'-flanking GRE and point mutagenesis

    PMID:12818426

    Open questions at the time
    • Reporter-based; endogenous chromatin occupancy shown only in later work
    • Tissue-specificity of the element not addressed
  5. 2004 High

    Demonstrated in vivo that Dexras1 couples NMDA and light input to Gi/o-ERK signaling to shape circadian entrainment.

    Evidence dexras1-/- mice with circadian behavioral assays, pertussis toxin epistasis, and ERK activation readouts

    PMID:15020218 PMID:15339652

    Open questions at the time
    • Molecular link from Dexras1 to ERK in the SCN not fully reconstituted
    • Relationship between Gαi and Gβγ arms incompletely defined
  6. 2006 High

    Resolved how NO-activated Dexras1 drives neuronal iron uptake by identifying the PAP7–DMT1 cascade, connecting the GTPase to excitotoxicity.

    Evidence Reciprocal Co-IP of Dexras1-PAP7 and PAP7-DMT1, iron uptake assays, and iron-chelation rescue of NMDA neurotoxicity

    PMID:16908409 PMID:17167088

    Open questions at the time
    • Stoichiometry and structure of the Dexras1–PAP7–DMT1 complex unknown
    • How activation triggers DMT1 recruitment mechanistically unclear
  7. 2008 Medium

    Extended Dexras1 into transcriptional control by showing it binds the FE65 PTB2 domain and suppresses FE65-APP-driven gene expression, including GSK3β and Tau effects.

    Evidence Co-IP, GST pulldown, luciferase reporter, and siRNA knockdown with Tau phosphorylation Western blots

    PMID:18922798

    Open questions at the time
    • GTPase-dependence of FE65 binding not dissected
    • In vivo relevance to APP biology not established
  8. 2011 Medium

    Defined nuclear and Gαi-monomer partners of Rasd1 (Ear2, NonO, GTP-Gαi) showing GTP-hydrolysis-dependent regulation of renin and CRE-dependent transcription.

    Evidence Yeast two-hybrid, pulldown, Co-IP from tissue, promoter-luciferase, ChIP, and GTP-Gαi pulldowns with nucleotide mutants

    PMID:21247419 PMID:21374700 PMID:21915321

    Open questions at the time
    • Whether nuclear and membrane functions occur in the same cells unclear
    • Direct vs indirect transcriptional effects not fully separated
  9. 2013 High

    Provided genetic proof that Dexras1 is required for NO-specific iron-mediated neuronal death and for adipogenesis, defining distinct physiologic outputs.

    Evidence Dexras1 knockout mice with stimulus-specific neuronal death and retinal protection assays, and 3T3-L1/MEF adipogenesis with in vivo diet-induced obesity

    PMID:23426685 PMID:24297897

    Open questions at the time
    • Molecular link between Dexras1 activation and adipogenic transcription not yet defined at this stage
    • Iron-death pathway downstream of DMT1 not fully traced
  10. 2015 Medium

    Revealed PKA phosphorylation of Ser253 as a counter-regulatory switch that suppresses S-nitrosylation and iron influx, establishing PTM crosstalk.

    Evidence In vitro PKA assay, Ser253 mutagenesis, S-nitrosylation detection, and iron influx assays with adiponectin treatment

    PMID:26358293

    Open questions at the time
    • Structural basis of phosphorylation–nitrosylation antagonism unknown
    • In vivo significance of Ser253 not tested
  11. 2016 Medium

    Mechanistically connected glucocorticoid/IGF-1 signaling to MAPK-driven adipogenesis through C-terminal membrane translocation and Shc/Raf binding, and identified TRPC4 activation as a Gαi-dependent output.

    Evidence C-terminal deletion mutants, membrane fractionation, Co-IP with Shc/Raf, C/EBPβ assays, and TRPC4 patch-clamp with Gαi epistasis

    PMID:25502319 PMID:26739966 PMID:27080392 PMID:27345868

    Open questions at the time
    • Direct GTPase activity state during membrane translocation not defined
    • Channel-gating mechanism for TRPC4 not resolved
  12. 2018 Medium

    Placed Dexras1 downstream of NMDA receptors in activity- and exercise-dependent neural progenitor recruitment and synaptic excitability control.

    Evidence dexras1-/- mice with exercise paradigm, BrdU assays, ERK/CREB and neurotrophin readouts, and NMDA antagonist epistasis; hippocampal slice electrophysiology

    PMID:27997888 PMID:29593295

    Open questions at the time
    • Cell-autonomous vs niche contributions not separated
    • Mechanism linking iron signaling to NR2A regulation incompletely defined
  13. 2025 Medium

    Demonstrated that SNO-Dexras1 limits recovery after CNS injury, with non-nitrosylatable Dexras1-C11S and knockdown promoting plasticity and recovery in stroke and white-matter injury.

    Evidence Photothrombotic stroke and SAH models with AAV/lentiviral manipulation, behavioral, electrophysiological, and morphological readouts

    PMID:31406150 PMID:36230939 PMID:39749632

    Open questions at the time
    • Therapeutic targeting strategies not validated
    • Relative contributions of iron vs cAMP arms in injury not dissected
  14. 2024 Medium

    Identified post-transcriptional and epigenetic silencing of RASD1 in cancer, linking its loss to cAMP/PKA/CREB-driven proliferation.

    Evidence MeRIP-seq/RIP/RNA-stability assays for KIAA1429–m6A–YTHDF2 in gastric cancer and ChIP/bisulfite sequencing for lncRNA SIX1-1–DNMT1 promoter methylation in cervical cancer

    PMID:38902717 PMID:39014290

    Open questions at the time
    • Whether RASD1 acts as a tumor suppressor in vivo not established
    • Direct GTPase signaling output suppressed in tumors not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct Dexras1 outputs — neuronal iron uptake, cAMP suppression, transcriptional partner regulation, and adipogenic membrane signaling — are coordinated by its activation state and subcellular localization within a single cell remains unresolved.
  • No structural model of Dexras1 in its active or partner-bound states
  • Unclear how PTM state dictates choice among competing effectors
  • Spatial segregation of nuclear vs membrane functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 3 GO:0003924 GTPase activity 2
Localization
GO:0005634 nucleus 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9909396 Circadian clock 2
Partners
CAPONDMT1FE65NONONOS1NR2F6PAP7SHC1
Complex memberships
nNOS–CAPON–Dexras1 ternary complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Dexras1 physically interacts with the nNOS adaptor protein CAPON, forming a ternary complex with nNOS and CAPON that enhances nNOS-mediated activation of Dexras1; Dexras1 is activated by NO donors and by NMDA receptor-stimulated NO synthesis in cortical neurons, establishing it as a physiologic NO effector downstream of nNOS. Co-immunoprecipitation (ternary complex), GTPase activation assays with NO donors and NMDA stimulation in cortical neurons, genetic validation using nNOS-/- mice showing selective reduction of Dexras1 activation Neuron High 11086993
2002 S-nitrosylation of Dexras1 occurs exclusively on Cys11; mutagenesis of Cys11 abolished NO donor-mediated activation of Dexras1, identifying this single residue as the site of NO-mediated guanine nucleotide exchange activation. Nitrosopeptide mapping (2D peptide chromatography of radiolabeled S-nitrosylated cysteines), site-directed mutagenesis of Cys11 Chemistry & biology High 12498886
2006 Dexras1 binds to PAP7 (peripheral benzodiazepine receptor-associated protein), which in turn binds DMT1 (divalent metal transporter 1), establishing a signaling cascade: NMDA receptor activation → nNOS → S-nitrosylation/activation of Dexras1 → PAP7 → DMT1 → iron uptake in neurons. Co-immunoprecipitation of Dexras1-PAP7 and PAP7-DMT1; functional iron uptake assays in cortical neurons; iron chelation rescue of NMDA neurotoxicity Neuron High 16908409
2004 Dexras1 couples NMDA receptor and light input to Gi/o and ERK activation in the suprachiasmatic nucleus (SCN); genetic deletion of Dexras1 eliminates a pertussis-sensitive circadian response to NMDA and reduces photic entrainment, while greatly potentiating nonphotic responses to neuropeptide Y and arousal. Gene-targeted dexras1-/- mice; circadian behavioral assays; pharmacological pertussis toxin treatment; ERK/MAPK activation assays Neuron High 15339652
2001 Dexras1 inhibits signal transduction from the Gi-coupled formyl peptide receptor (FPR) to ERK1/2; while Dexras1 alone weakly activates ERK2, it attenuates ligand-stimulated FPR-to-ERK signaling and impairs pertussis toxin-catalyzed ADP-ribosylation of membrane Gi-alpha, suggesting it acts very proximally at receptor-Gi coupling. Co-transfection of Dexras1 and FPR in COS-7 and HEK293 cells; immune complex in vitro kinase assay for HA-Erk-2; GTPγS binding assay; ADP-ribosylation assay The Journal of biological chemistry High 11751935
2001 Constitutively active Dexras1 (A178V mutant) inhibits cAMP-stimulated peptide hormone secretion in AtT-20 corticotroph cells; this inhibition requires prenylation, as deletion of the CAAX box (C277term) abolishes the effect. Wild-type Dexras1 had no effect on cAMP-stimulated secretion. Transient co-transfection with human GH secretion reporter; 8-Br-cAMP stimulation assay; GTP-binding assay of wild-type and mutant Dexras1; CAAX deletion mutagenesis Endocrinology High 11356714
2004 Dexras1 inhibits adenylyl cyclase activity in a pertussis toxin-sensitive and RGS4-sensitive manner, but independently of dominant-interfering Gi-alpha2 mutants, indicating it activates both Gi-alpha- and Gβγ-dependent arms of Gi signaling. Dexras1 also decreases forskolin-stimulated CREB activation. cAMP measurement assays in cells co-expressing constitutively active Gsα(Q227L) and Dexras1; pertussis toxin treatment; RGS4 co-expression; dominant-interfering Gi mutants; CREB-luciferase reporter Biochemical and biophysical research communications Medium 15020218
2005 Dexras1 blocks Gβγ-dependent heterologous sensitization of adenylyl cyclase 1 (AC1) induced by persistent D2L receptor activation; this block requires nucleotide binding, as the Dexras1-G31V mutant is without effect. Dexras1 also reduces D2L receptor-mediated ERK1/2 activation by ~50% but does not alter acute D2L receptor inhibition of AC1. cAMP assay in HEK293 cells; ERK1/2 phosphorylation assay; betaARK-ct Gβγ scavenger experiment; Dexras1-G31V nucleotide-binding mutant Biochemical and biophysical research communications Medium 15913563
2003 A glucocorticoid response element (GRE) in the 3'-flanking region (~2.3 kb downstream of the poly(A) signal) of the human Dexras1 gene is required for rapid glucocorticoid-induced transcription; a point mutation in the 15-bp GRE abolishes glucocorticoid responsiveness. Luciferase reporter assay with GRE-containing 3'-flanking region; site-directed point mutagenesis of GRE Biochimica et biophysica acta Medium 12818426
2008 Dexras1 binds to the PTB2 domain of the adaptor protein FE65 and potently suppresses FE65-APP intracellular domain-mediated transcription (including GSK3β); Dexras1 and APP can simultaneously bind FE65 PTB2. Phosphorylation of FE65 Tyr547 reduces Dexras1-FE65 binding. siRNA knockdown of Dexras1 enhances GSK3β expression and increases Tau phosphorylation. Co-immunoprecipitation; GST pulldown; luciferase transcription reporter; siRNA knockdown; Western blot for Tau phosphorylation The Journal of biological chemistry Medium 18922798
2013 Dexras1 is required for NO-mediated (but not H2O2- or staurosporine-mediated) iron influx and neuronal death; deletion of Dexras1 in mice attenuates NO-mediated cell death in primary cortical neurons and protects retinal ganglion cells in vivo from NMDA excitotoxicity. Dexras1 knockout mice; primary cortical neuron cultures; retinal ganglion cell survival assays in vivo; iron chelation experiments; cell death assays with multiple apoptotic stimuli The Journal of neuroscience High 23426685
2013 Dexras1 is required for adipogenesis; depletion of Dexras1 abolishes adipogenic differentiation of 3T3-L1 cells, overexpression elicits adipogenesis, and Dexras1-deleted mice show reduced adiposity and diminished diet-induced weight gain. Dexras1 knockdown and overexpression in 3T3-L1 cells; mouse embryonic fibroblasts from Dexras1-/- mice; in vivo diet-induced obesity model Proceedings of the National Academy of Sciences of the United States of America High 24297897
2016 Dexras1 mediates adipogenesis downstream of glucocorticoids by linking to IGF-1 signaling: upon insulin/IGF-1 treatment, Dexras1 translocates to the plasma membrane via its unique C-terminal domain (aa 223–276), activates MAPK through interaction with Shc and Raf, and drives CCAAT/enhancer binding protein β (C/EBPβ) phosphorylation and mitotic clonal expansion. Dexras1 C-terminal deletion mutants; plasma membrane fractionation/subcellular localization; Co-IP of Dexras1 with Shc and Raf; MAPK phosphorylation assays; C/EBPβ phosphorylation assays Scientific reports Medium 27345868
2015 PKA phosphorylates Dexras1 on Ser253, which suppresses iron influx by reducing S-nitrosylation of Dexras1 in a dose-dependent manner; adiponectin modulates Dexras1 iron trafficking via PKA. This establishes a functional crosstalk between S-nitrosylation and phosphorylation on Dexras1. In vitro PKA phosphorylation assay; site-directed mutagenesis (Ser253); S-nitrosylation detection assay; iron influx assay; adiponectin treatment FEBS letters Medium 26358293
2011 Dexras1 (AGS1) decreases cAMP accumulation downstream of dopamine D1 receptor signaling independently of pertussis toxin (suggesting interaction with a Gα-i monomer rather than the heterotrimeric Gi complex), and both AGS1/Dexras1 and Rhes associate with GTP-bound Gα-i in pull-down assays. Neither protein interacted with the D1 receptor directly. cAMP accumulation assay in transfected cells; pertussis toxin treatment; GTP-Gα-i pull-down assay Journal of neuroscience research Medium 21374700
2011 Rasd1 interacts with Ear2 (Nr2f6), a nuclear receptor/negative regulator of renin transcription, via the ligand binding domain of Ear2; this interaction inhibits Ear2-mediated transcriptional repression and upregulates endogenous renin transcription. Missense mutations in Rasd1 that attenuate Ear2 binding also abolish the functional effect. GTP-hydrolysis activity of Rasd1 is required. Yeast two-hybrid screen; in vitro pulldown; Co-IP in COS-7 cells and from mouse brain/HEK293T lysates; renin promoter-luciferase reporter; real-time RT-PCR; shRNA knockdown; domain mapping with Ear2 deletion mutants BMC molecular biology Medium 21247419
2011 Rasd1 interacts with NonO (p54nrb) via affinity pulldown and Co-IP; the GTP-hydrolysis activity of Rasd1 is required for functional interaction. Rasd1 modulates NonO coactivator function at CRE-site-containing target genes in the cAMP pathway, as shown by reporter gene assays and chromatin immunoprecipitation. Affinity pulldown; co-immunoprecipitation; indirect immunofluorescence; luciferase reporter gene assays; chromatin immunoprecipitation; gene knockdown PloS one Medium 21915321
2006 Dexras1 limits the capacity of PACAP/PAC1 to affect ERK/MAPK in the SCN during the late night, and modulates light-induced ERK/MAPK in a time-of-day-specific manner; daytime photic phase advances are mediated by a pathway that stimulates ERK/MAPK in the SCN shell and triggers downregulation of clock protein expression, all dependent on Dexras1. dexras1-/- mice; circadian behavioral phase response curve analysis; ERK/MAPK phosphorylation assays; clock protein immunohistochemistry in SCN The Journal of neuroscience High 17167088
2012 Glucocorticoid receptor (GR) and STAT5b cooperatively drive glucocorticoid-induced Rasd1 expression in pancreatic islets; prolactin inhibits this GR/STAT5b transcriptional activity on the Rasd1 gene. Rasd1 knockdown abolishes the inhibitory effects of dexamethasone on insulin secretion and on PKA, PKC, and ERK1/2 pathways in β-cells. Chromatin immunoprecipitation (GR and STAT5b on Rasd1 promoter); siRNA knockdown of Rasd1; insulin secretion assay; Western blot of PKA, PKC, ERK1/2 phosphorylation; immunofluorescence localization in β-cells Endocrinology Medium 22700767
2014 Dexras1 activates TRPC4 channels when co-expressed; among Ras family members tested, Rasd1 is uniquely capable of activating TRPC4, and this requires functional Gαi1 and Gαi3. Dexamethasone increases Rasd1 protein expression in INS-1 cells and thereby triggers TRPC4-like cationic current. Electrophysiology (patch-clamp) of TRPC4 currents in cells co-expressing Rasd1 and other Ras family members; Gαi1/Gαi3 co-expression experiments; dexamethasone treatment of INS-1 cells with current recording Pflugers Archiv : European journal of physiology Medium 25502319
2016 Genetic and pharmacological ablation of the Dexras1-mediated neuronal iron pathway increases glutamatergic transmission; lysosomal iron is identified as the main source for iron signaling that modulates NMDA receptor activity via the PKC/Src/NR2A pathway, establishing Dexras1 as a modulator of synaptic excitability. Dexras1-/- mice; voltage-sensitive dye imaging of hippocampal slices; whole-cell patch-clamp of synaptic NMDA currents; pharmacological iron chelation; Western blot for NR2A and PKC/Src pathway components Molecular brain Medium 27080392
2016 Rasd1 inhibits cAMP-induced gene expression (c-Fos, Nr4a1, pCREB) in AtT20 cells and in rat supraoptic nucleus neurons; these effects are dependent on isoprenylation, as farnesyltransferase inhibitor FTI-277 and CAAX box deletion prevent inhibition. In vivo lentiviral Rasd1 overexpression in rat SON diminishes cAMP-inducible genes under osmotic stress. Rasd1 overexpression and shRNA knockdown in AtT20 cells; dexamethasone treatment; FTI-277 treatment; CAAX deletion mutant; lentiviral injection into rat supraoptic nucleus; Western blot and immunofluorescence for CREB phosphorylation and target genes Molecular brain Medium 26739966
2016 RASD1 knockdown in mouse GV oocytes arrests meiotic maturation at metaphase I, causing disrupted spindle formation and chromosomal misalignment; the MI-to-MII transition factors Obox4 and Arp2/3 are misregulated by Rasd1 knockdown, revealing a role for RASD1 in cytokinesis progression and spindle formation during oocyte maturation. RNAi microinjection into mouse GV oocytes; time-lapse video microscopy; immunofluorescence for spindle and chromosomes; qRT-PCR for Obox4 and Arp2/3 Cellular physiology and biochemistry Medium 27997888
2018 Dexras1 is required for exercise-triggered recruitment of quiescent neural progenitors into the cell cycle in the hippocampal neurogenic niche; dexras1-/- mice show abolished exercise-dependent ERK/MAPK and CREB activation, impaired NR2A upregulation, and reduced bdnf/trkB/vegf-a induction in the dentate gyrus. NMDA receptor pharmacological inhibition enhances SGZ proliferation in wild-type but not dexras1-/- mice, placing Dexras1 downstream of NMDA receptors in this pathway. dexras1-/- mice; exercise paradigm; BrdU incorporation/cell survival assays; Western blot for ERK/MAPK, CREB; RT-PCR for NR2A, bdnf, trkB, vegf-a; NMDA receptor antagonist pharmacology Scientific reports Medium 29593295
2019 Dexras1 deletion attenuates oxidative stress-induced neurodegeneration in experimental optic neuritis (EAE model); Dexras1 is activated by S-nitrosylation by both iNOS (in activated microglia/macrophages) and nNOS (in neurons), and iron entry triggered by NO-activated Dexras1 contributes to retinal ganglion cell and axonal loss during optic neuritis. Dexras1-/- mice in EAE model; visual function assessment; retinal ganglion cell and axon counting; iron chelator (deferiprone) treatment Scientific reports Medium 31406150
2025 S-nitrosylation of Dexras1 (SNO-Dexras1) is elevated in peri-infarct cortex after stroke; AAV-mediated knockdown of Dexras1 or overexpression of dominant-negative Dexras1-C11S (non-nitrosylatable) promotes motor recovery, increases neuronal excitability (spike number and mEPSC frequency), and enhances dendritic spine density in peri-infarct cortex. Conversely, Dexras1 overexpression worsens stroke outcome. Photothrombotic stroke model in mice; AAV microinjection (Dexras1 KD, Dexras1-C11S overexpression, Dexras1 overexpression); grid-walking and cylinder behavioral tasks; Western blot for SNO-Dexras1; electrophysiology (spike recording, mEPSC); Golgi staining for dendritic spines CNS neuroscience & therapeutics Medium 39749632
2022 Dexras1 induces oligodendrocyte dysdifferentiation and myelin injury after subarachnoid hemorrhage by inhibiting the cAMP-CREB pathway; Dexras1 overexpression worsens OPC dysdifferentiation while knockdown ameliorates myelin injury and glial activation after SAH. Intracerebroventricular lentiviral Dexras1 overexpression/knockdown in SAH rat model; immunofluorescence; transmission electron microscopy; Western blot for cAMP-CREB pathway components; primary neuron treatment with oxyhemoglobin Cells Medium 36230939
2024 KIAA1429 increases the m6A modification level of RASD1 mRNA and enhances its degradation in an m6A-YTHDF2-dependent manner, thereby downregulating RASD1 expression in gastric cancer cells. MeRIP-seq; MeRIP-qPCR; RNA stability assay; RNA immunoprecipitation (RIP); RNA pull-down; dual luciferase reporter; Western blot Journal of translational medicine Medium 38902717
2024 The lncRNA SIX1-1 promotes cervical cancer cell proliferation by recruiting DNMT1 to the RASD1 promoter, causing its methylation and transcriptional silencing; reduced RASD1 expression then activates the cAMP/PKA/CREB signaling pathway to promote proliferation. SIX1-1 knockdown in vitro and in vivo; nuclear localization by fractionation; Co-IP/binding of SIX1-1 with DNMT1; chromatin immunoprecipitation (DNMT1 on RASD1 promoter); bisulfite sequencing; RASD1 rescue experiments Human cell Medium 39014290

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 272 11086993
2006 NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Neuron 225 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
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
2013 Dexras1, a small GTPase, is required for glutamate-NMDA neurotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience 61 23426685
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
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 48 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 Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation. Molecular brain 35 26739966
2016 Lysosomal iron modulates NMDA receptor-mediated excitation via small GTPase, Dexras1. Molecular brain 34 27080392
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
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 26 29722068
2019 Dexras1 Deletion and Iron Chelation Promote Neuroprotection in Experimental Optic Neuritis. Scientific reports 23 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 21 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 Rapid expression of RASD1 is regulated by estrogen receptor-dependent intracellular signaling pathway in the mouse uterus. Molecular and cellular endocrinology 17 28188843
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
2014 Small G Proteins Dexras1 and RHES and Their Role in Pathophysiological Processes. International journal of cell biology 16 24817889
2018 Dexras1 is a homeostatic regulator of exercise-dependent proliferation and cell survival in the hippocampal neurogenic niche. Scientific reports 15 29593295
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 Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating. Neuroscience 12 26946266
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
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
2015 The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels. Channels (Austin, Tex.) 7 26083271
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
2017 Rasd1 is an estrogen-responsive immediate early gene and modulates expression of late genes in rat anterior pituitary cells. Endocrine journal 6 28835591
2016 Circadian Dexras1 in rats: Development, location and responsiveness to light. Chronobiology international 6 26785766
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
2021 Expression of Rasd1 in mouse endocrine pituitary cells and its response to dexamethasone. Stress (Amsterdam, Netherlands) 5 33840368
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
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
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

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