Affinage

RASSF5

Ras association domain-containing protein 5 · UniProt Q8WWW0

Length
418 aa
Mass
47.1 kDa
Annotated
2026-06-10
53 papers in source corpus 25 papers cited in narrative 25 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

RASSF5 (NORE1/RAPL) is a non-catalytic scaffold that couples Ras-family GTPase signaling to the pro-apoptotic Hippo-related kinases MST1/2, linking growth-factor and adhesion cues to apoptosis, cell-cycle control, and cytoskeletal polarity (PMID:9488663, PMID:15109305, PMID:20810663). It binds GTP-loaded Ras through its RA domain following EGF receptor activation (PMID:9488663) and engages MST1/2 through SARAH-domain heterodimerization (PMID:15109305, PMID:23972470). Structural work resolves the regulatory logic: in the inactive state an intramolecular C1–RA complex occludes the RA domain and renders the SARAH domain self-associated and autoinhibited, while GTP-Ras binding disrupts the C1–RA complex, exposing a phosphatidylinositol-3-phosphate-binding C1 interface and freeing SARAH to heterodimerize with MST kinases (PMID:16698549, PMID:23972470). RASSF5 acts as a timing-dependent switch on MST2—its SARAH domain disrupts the MST2 homodimer to block trans-autophosphorylation when bound before activation, yet does not inhibit already-activated kinase, allowing it to be either inhibitor or positive regulator (PMID:23972470, PMID:15109305). Through MST1, RASSF5 mediates death-receptor (TNF-α/TRAIL)-induced apoptosis and suppresses transformation, with Rassf5-null cells immortalizing and becoming transformable by K-RasG12V (PMID:20810663). As the Rap1/Rap2 effector RAPL, it scaffolds a Rap1–SKAP1–RAPL–LFA-1 complex that, with MST1, spatially redistributes LFA-1 to the leading edge to drive lymphocyte adhesion, polarity, and trafficking (PMID:12845325, PMID:16892067, PMID:20346707), and it independently restrains lymphocyte proliferation by promoting nuclear localization of p27kip1 (PMID:21194982). RASSF5 stability and localization are tightly controlled: acetylation-gated, Itch-mediated ubiquitination governs its turnover (PMID:23538446), and Lck-dependent tyrosine phosphorylation controls its CRM1-dependent nucleocytoplasmic shuttling and pro-apoptotic activity (PMID:20064523). At the transcriptional level its expression is set by chromatin regulators including Jmjd3-mediated H3K27me3 removal and Irf8-driven activation during granulopoiesis (PMID:31092054, PMID:37247756).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1998 High

    Established RASSF5 as a candidate Ras effector by showing direct GTP-dependent Ras binding, defining the entry point linking it to Ras signaling.

    Evidence GTP-dependent in vitro binding assay and co-IP after EGF stimulation in COS-7 and KB cells

    PMID:9488663

    Open questions at the time
    • Did not define a downstream effector function
    • No structural basis for binding
  2. 2002 High

    Showed RASSF5 hetero-oligomerizes with RASSF1A and that RASSF1A reaches active Ras indirectly via RASSF5, positioning RASSF5 as the direct Ras-sensing member of a scaffold network.

    Evidence Reciprocal co-IP with domain-deletion constructs in COS cells

    PMID:11857081

    Open questions at the time
    • Functional consequence of the heterodimer not resolved
  3. 2003 High

    Identified RASSF5/RAPL as a Rap1 effector controlling integrin function, extending its GTPase scaffolding role from apoptosis into lymphocyte adhesion and polarity.

    Evidence Co-IP, immunofluorescence, adhesion assays in lymphocytes after TCR/CXCL12 stimulation

    PMID:12845325

    Open questions at the time
    • Did not identify the kinase partner mediating LFA-1 redistribution
  4. 2004 High

    Connected RASSF5 to MST1 and demonstrated bidirectional regulation—inhibiting autoactivation in solution but promoting activation at the membrane—revealing the Ras→RASSF5→MST apoptotic axis.

    Evidence Endogenous co-IP, in vitro kinase assay with purified proteins, membrane-targeting constructs

    PMID:15109305

    Open questions at the time
    • Structural basis of homodimer disruption not yet defined
    • Physiological trigger for the inhibitor-to-activator switch unclear
  5. 2004 High

    Genetic loss-of-function in mice established RAPL as essential for chemokine-triggered lymphocyte and dendritic cell adhesion and in vivo trafficking.

    Evidence RAPL-knockout mouse, adhesion and in vivo trafficking assays

    PMID:15361866

    Open questions at the time
    • Molecular link between Rap1, RAPL and LFA-1 redistribution not fully mapped
  6. 2004 Medium

    Showed RASSF5 growth suppression can be independent of its MST-, Ras-, and zinc-finger domains, implying additional uncharacterized effector routes.

    Evidence Colony formation and soft-agar assays with domain-deletion mutants

    PMID:15007383

    Open questions at the time
    • The domain-independent effector was not identified
    • Single lab, no pathway mapping
  7. 2004 Medium

    Demonstrated Rap1-driven release of RAPL from microtubules to the leading edge, linking GTPase activation to cytoskeletal repositioning during directional migration.

    Evidence Live GFP imaging, FRET Rap1 probe, rap1GAPII expression, wound-healing assay in endothelial cells

    PMID:15569673

    Open questions at the time
    • Mechanism of microtubule association not defined
    • Single lab
  8. 2006 High

    Established MST1 as the obligate kinase partner for RAPL-driven LFA-1 clustering, unifying the adhesion and Hippo-kinase functions of RASSF5.

    Evidence Co-IP, siRNA knockdown, co-localization, kinase and adhesion assays

    PMID:16892067

    Open questions at the time
    • How MST1 kinase activity drives LFA-1 clustering mechanistically unresolved
  9. 2006 High

    Defined the autoinhibitory C1–RA intramolecular complex and its disruption by GTP-Ras, providing the structural switch that gates RASSF5 activity and lipid binding.

    Evidence NMR structure of C1 domain, ITC, chemical shift/relaxation measurements in mouse Nore1

    PMID:16698549

    Open questions at the time
    • Did not directly link C1 release to SARAH/MST engagement
    • Membrane context not tested
  10. 2007 Medium

    Showed RASSF5 binds Rap2 and classical Ras more stably than Rap1 and that SARAH mediates its homodimerization, refining GTPase selectivity and the oligomeric basis of signaling.

    Evidence Co-IP, mutagenesis, 3D modeling, adhesion/migration assays

    PMID:17716979

    Open questions at the time
    • Functional preference among GTPases in vivo not resolved
    • Single lab
  11. 2010 High

    Identified an MST-independent proliferation control: RAPL drives p27kip1 nuclear localization to restrain lymphocyte cycling, with loss causing autoimmunity and lymphoma.

    Evidence RAPL-knockout mouse, p27 Ser10 phospho-analysis, S10A knock-in rescue, Cdk2 assay

    PMID:21194982

    Open questions at the time
    • How RAPL inhibits p27 Ser10 phosphorylation mechanistically unknown
  12. 2010 High

    Demonstrated RASSF5 mediates death-receptor apoptosis through MST1 and acts as a tumor suppressor restraining Ras transformation.

    Evidence siRNA knockdown, Rassf5-knockout mice and MEFs, apoptosis and transformation assays

    PMID:20810663

    Open questions at the time
    • Connection between death-receptor engagement and RASSF5 activation undefined
  13. 2010 Medium

    Mapped NES/NLS signals and Lck-dependent phosphorylation controlling nucleocytoplasmic shuttling, tying subcellular localization to RASSF5's cell-cycle and apoptotic outputs.

    Evidence Heterokaryon shuttling, leptomycin B, mutagenesis, Lck co-IP, flow cytometry

    PMID:20064523

    Open questions at the time
    • Nuclear substrates/targets of RASSF5 not identified
    • Single lab
  14. 2010 High

    Defined SKAP1 as a SARAH-binding partner required to deliver the Rap1–RapL–LFA-1 complex and modulate T cell motility, completing the adhesion-complex architecture.

    Evidence Skap1-knockout T cells, co-IP, L224A mutagenesis, intravital imaging

    PMID:20346707

    Open questions at the time
    • Stoichiometry and dynamics of the full complex not resolved
  15. 2011 Medium

    Showed SKAP1's PH domain drives PI3K-dependent membrane recruitment of RapL, defining the membrane-targeting step that activates LFA-1.

    Evidence Co-IP, membrane fractionation, PH-domain mutation, myr-SKAP1 construct, LFA-1–ICAM-1 binding

    PMID:21669874

    Open questions at the time
    • Interplay with the C1 lipid-binding interface not tested
    • Single lab
  16. 2012 Medium

    Revealed a scaffolding role beyond MST: RASSF5 bridges HIPK1 to Mdm2 to promote its ubiquitination, expanding its tumor-suppressive output.

    Evidence Endogenous co-IP, ubiquitination assay, Nore1-knockout MEFs, tumor assay

    PMID:22173032

    Open questions at the time
    • Regulation of this scaffold function unknown
    • Single lab
  17. 2013 High

    Crystal structures of Mst2±RASSF5 SARAH explained the timing-dependent switch: RASSF5 disrupts the Mst2 activating homodimer only before activation-loop phosphorylation, otherwise leaving the active kinase intact.

    Evidence X-ray crystallography of Mst2 and Mst2–RASSF5 SARAH, kinase assay, mutagenesis

    PMID:23972470

    Open questions at the time
    • What determines binding timing in cells not defined
  18. 2013 High

    Characterized the Nore1 SARAH homodimer as a lower-affinity antiparallel coiled coil relative to MST1, clarifying the thermodynamic basis for hetero- versus homo-dimer preference.

    Evidence X-ray crystallography, CD/DSF stability, analytical ultracentrifugation

    PMID:23331050

    Open questions at the time
    • Cellular consequence of differential SARAH stability not tested
  19. 2013 Medium

    Identified acetylation-gated Itch-mediated ubiquitination as the route controlling RASSF5 protein stability and its apoptotic/cell-cycle activity.

    Evidence Co-IP, ubiquitination assay, acetylation analysis, ligase-dead control, flow cytometry

    PMID:23538446

    Open questions at the time
    • Acetyltransferase/deacetylase governing the switch not identified
    • Single lab
  20. 2014 High

    Showed MST2 SARAH homodimerization and RAPL heterodimerization are both required for full kinase activation and T cell apoptosis, integrating structure with function.

    Evidence X-ray crystallography, structure-guided mutagenesis, kinase and apoptosis assays

    PMID:24468289

    Open questions at the time
    • Order of homo- and hetero-dimerization events in vivo unresolved
  21. 2014 Medium

    Placed RASSF5 upstream of Ndr1/2 kinases in neuronal polarization via Par3 Ser383 phosphorylation, broadening its kinase-scaffold repertoire beyond MST.

    Evidence Neuronal shRNA, Ndr→Par3 phosphorylation assay, axon specification in hippocampal neurons

    PMID:24928906

    Open questions at the time
    • How RASSF5 engages Ndr kinases mechanistically undefined
    • Single lab
  22. 2017 Low

    Computational modeling proposed that the RA domain holds the SARAH domain in a kinked autoinhibited state relieved by K-Ras4B-GTP at the membrane, integrating the structural switch model.

    Evidence All-atom molecular dynamics simulations from crystal structures (no experimental validation)

    PMID:28197608

    Open questions at the time
    • Computational only; awaits experimental validation
    • Membrane requirement not tested biochemically
  23. 2019 Medium

    Established chromatin-level control of RASSF5 by Jmjd3-mediated H3K27me3 removal, linking epigenetic regulation to RASSF5-dependent apoptosis.

    Evidence ChIP for H3K27me3, Jmjd3 shRNA, qRT-PCR, apoptosis assays in osteoblasts

    PMID:31092054

    Open questions at the time
    • Whether this regulation operates in cancer cells not tested
    • Single lab
  24. 2021 Medium

    Engineered high-affinity RA-domain variants showed that boosting Ras engagement simultaneously suppresses pro-cancer pathways and activates RASSF5 anti-cancer (senescence, p53) outputs, validating the effector axis as a therapeutic node.

    Evidence Computational design plus in vitro evolution, viability/migration/senescence assays, p53 modification blots in A549

    PMID:34717958

    Open questions at the time
    • Mechanism linking RA binding to p53 modification not defined
    • Single lab
  25. 2023 Medium

    Defined an Irf8→RASSF5 transcriptional axis restraining emergency granulopoiesis, with loss driving clonal hematopoiesis and AML, extending its tumor-suppressor role to myeloid biology.

    Evidence Rassf5-knockout mouse, Irf8 ChIP/transcription assays, clonal hematopoiesis analysis

    PMID:37247756

    Open questions at the time
    • Downstream effector mediating granulopoiesis control unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple inputs—GTPase loading, lipid binding, SKAP1/membrane recruitment, Lck phosphorylation, and acetylation/ubiquitination—are integrated to determine whether RASSF5 inhibits or activates MST kinases in a given cellular context remains unresolved.
  • No unified model of context-dependent inhibitor-versus-activator switching
  • Endogenous timing of SARAH binding relative to MST activation in cells not measured
  • Domain-independent growth-suppressive effector still unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2
Partners
HRASITCHLCKMST1RAP1SKAP1STK3STK4
Complex memberships
RASSF5-MST1/2 SARAH heterodimerRap1-SKAP1-RapL-LFA-1 complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 RASSF5/Nore1 directly interacts with active (GTP-bound) Ras in vitro in a manner requiring an intact Ras effector domain, and associates with Ras in situ following EGF receptor activation in COS-7 and KB cells, identifying it as a potential Ras effector. In vitro binding assay (GTP-dependent), co-immunoprecipitation after EGF stimulation The Journal of biological chemistry High 9488663
2002 RASSF5/Nore1A homodimerizes and heterodimerizes with RASSF1A through their non-homologous N-terminal segments; RASSF1A association with RasG12V in COS cells is indirect, mediated by its heterodimerization with Nore1A via Nore1A's RA domain. Co-immunoprecipitation in COS cells; domain-deletion and co-expression experiments Oncogene High 11857081
2003 RASSF5/RAPL is a Rap1 effector that associates with active Rap1 after TCR and CXCL12 stimulation; it binds LFA-1 and mediates Rap1-triggered spatial redistribution of LFA-1 to the leading edge, stimulating lymphocyte polarization and adhesion to ICAM-1. Co-immunoprecipitation, immunofluorescence localization, overexpression in lymphocytes, adhesion assays Nature immunology High 12845325
2004 Endogenous MST1 immunoprecipitates with RASSF5/NORE1A from KB cells; recombinant NORE1A directly inhibits MST1 autoactivation in vitro by suppressing Thr183 autophosphorylation; membrane-targeted NORE1A or recruitment of MST1 to Ras(G12V) via NORE1A increases MST1 Thr183 phosphorylation. Endogenous co-IP, in vitro kinase assay with purified proteins, co-transfection with CAAX/myristoylation constructs The Biochemical journal High 15109305
2004 RASSF5/RAPL deficiency in mice causes defective chemokine-triggered lymphocyte adhesion and impaired migration to secondary lymphoid organs; dendritic cells from RAPL-deficient mice also show defective adhesion and fail to migrate to lymph nodes after inflammatory stimulation. RAPL-knockout mouse model, adhesion assays, in vivo trafficking experiments, histology Nature immunology High 15361866
2004 RASSF5/Nore1A and Nore1B suppress colony formation and anchorage-independent growth in specific tumor cell lines; growth inhibition by Nore1A is independent of its MST-binding domain, Ras-binding domain, and zinc-finger, indicating growth suppression through unidentified effectors. Colony formation assay, soft agar assay, domain-deletion mutants, cell cycle analysis Oncogene Medium 15007383
2004 RASSF5/RAPL localizes on microtubules in endothelial cells; activated Rap1 induces dissociation of RAPL from microtubules and its redistribution to the leading edge, controlling directional cell migration; disruption of Rap1-RAPL interaction perturbs wound healing. Fluorescence live imaging (GFP-RAPL), FRET-based Rap1 activation probe, adenoviral expression of rap1GAPII, wound healing assay The Journal of biological chemistry Medium 15569673
2006 RASSF5/RAPL binds and regulates the localization and kinase activity of Mst1; RAPL and Mst1 co-localize in vesicular compartments and translocate together with LFA-1 to the leading edge upon Rap1 activation; Mst1 knockdown abolishes RAPL-induced LFA-1 clustering, cell polarization, and adhesion. Co-immunoprecipitation, siRNA knockdown, immunofluorescence co-localization, kinase activity assay, adhesion assay Nature immunology High 16892067
2006 In mouse Nore1, the C1 domain forms an intramolecular complex with the RA domain that weakens Ras/Rap1-GTP binding; GTP-Ras binding to the RA domain disrupts this C1-RA intramolecular complex, making the C1 domain's lipid-binding interface accessible; the free C1 domain binds phosphatidylinositol 3-phosphate. NMR structure of C1 domain, isothermal calorimetric titration (ITC), chemical shift and relaxation rate measurements Structure High 16698549
2007 RASSF5/RAPL forms more stable complexes with Rap2 and classical Ras than with Rap1; the SARAH domain mediates RAPL homodimerization in vitro and in cells; a single residue in switch I of Rap proteins (residue 39) critically determines the different interaction kinetics with RAPL; RAPL acts downstream of Rap2 in integrin-triggered T cell migration. Co-immunoprecipitation, mutagenesis, 3D modeling, adhesion and migration assays The Journal of biological chemistry Medium 17716979
2010 RASSF5/RAPL suppresses lymphocyte proliferation by promoting nuclear localization of p27kip1: RAPL inhibits phosphorylation of p27kip1 on Ser10, thereby promoting its nuclear translocation; RAPL-deficient mice show cytoplasmic mislocalization of p27kip1, hyperproliferation, enhanced Cdk2 activity, and develop lupus-like disease and B cell lymphoma. RAPL-knockout mouse, flow cytometry (cell cycle), kinase assay (Cdk2), immunofluorescence localization of p27kip1, S10A knock-in rescue experiment Immunity High 21194982
2010 RASSF5/NORE1 mediates death receptor (TNF-α, TRAIL)-induced apoptosis through its interaction with MST1; siRNA depletion of RASSF5 reduces TNF-α-mediated apoptosis and Mst1 activation; Rassf5-null mice are resistant to TNF-α-induced apoptosis; Rassf5-null MEFs spontaneously immortalize and are transformable by K-RasG12V. siRNA knockdown, Rassf5-knockout mouse, MEF immortalization and transformation assays, apoptosis assays The Journal of biological chemistry High 20810663
2010 RASSF5/RAPL contains functional nuclear export signal (NES, aa 260–300) dependent on CRM-1, and two nuclear localization signals; Lck tyrosine kinase binds RASSF5 through its C-terminal SH2-binding motif and phosphorylates it, which is required for efficient nuclear import of RASSF5; nuclear-localized (ΔNES) RASSF5 causes G1/S arrest and apoptosis, while an Lck-interaction-defective mutant induces apoptosis without cell cycle arrest. Heterokaryon shuttling assay, leptomycin B treatment, mutational analysis, immunofluorescence, co-immunoprecipitation with Lck, flow cytometry (cell cycle/apoptosis) Journal of molecular biology Medium 20064523
2010 SSKAP1 N-terminal domain binds the C-terminal SARAH domain of RASSF5/RapL; TCR-induced Rap1-RapL complex formation and LFA-1 binding fails in Skap1−/− T cells; a RapL mutation (L224A) abrogating SKAP1 binding disrupts colocalization in vesicles and T cell–DC conjugation; RapL expression slows T cell motility in lymph nodes. Skap1 knockout primary T cells, co-immunoprecipitation, point mutagenesis, intravital imaging of T cells in lymph nodes Immunity High 20346707
2011 SKAP1 PH domain is required for RapL membrane translocation in a PI3K-dependent manner; membrane-targeted (myristoylated) SKAP1 constitutively recruits RapL to membranes and promotes Rap1 and LFA-1 binding, substituting for PI3K and TCR ligation in LFA-1 activation. Co-immunoprecipitation, membrane fractionation, PH-domain point mutation (R131M), myr-SKAP1 constitutive construct, LFA-1–ICAM-1 binding assay The Journal of biological chemistry Medium 21669874
2012 RASSF5/NORE1 facilitates polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by scaffolding its interaction with the Mdm2 E3 ubiquitin ligase; endogenous HIPK1 is stabilized in Nore1-deficient MEFs. Co-immunoprecipitation (endogenous), ubiquitination assay, Nore1-knockout MEFs, in vivo tumor formation assay EMBO reports Medium 22173032
2013 Crystal structures of human Mst2 alone and in complex with RASSF5 SARAH domain reveal that: (i) Mst2 activates by transautophosphorylation at its activation loop requiring SARAH-mediated homodimerization; (ii) RASSF5 SARAH disrupts the Mst2 homodimer and blocks Mst2 autoactivation when bound before activation-loop phosphorylation; (iii) RASSF5 binding to already-activated Mst2 does not inhibit kinase activity—suggesting RASSF5 can be either inhibitor or positive regulator depending on the timing of binding relative to Mst2 activation. X-ray crystallography (Mst2 alone and Mst2–RASSF5 SARAH complex), in vitro kinase assay, mutagenesis Structure High 23972470
2013 The SARAH domain of RASSF5/Nore1 crystallizes as an antiparallel homodimeric coiled coil with heptad register interrupted by two stutters; the Nore1 SARAH homodimer has lower affinity and thermodynamic stability than the MST1 SARAH homodimer; the SARAH domain undergoes association-dependent folding. X-ray crystallography of SARAH homodimer, thermodynamic stability measurements (CD, DSF), analytical ultracentrifugation Biochemistry High 23331050
2013 E3 ubiquitin ligase Itch binds RASSF5 through its WW domains interacting with the PPxY motif of RASSF5; Itch overexpression induces RASSF5 poly-ubiquitination and proteasomal degradation; acetylation of RASSF5 in tumor cells blocks Itch binding, stabilizing RASSF5; inhibition of RASSF5 acetylation restores Itch binding and triggers degradation; Itch overexpression (but not ligase-dead mutant) abrogates RASSF5-mediated G1 arrest and apoptosis. Co-immunoprecipitation (in vivo and in vitro), ubiquitination assay, flow cytometry (cell cycle/apoptosis), acetylation analysis Cell death & disease Medium 23538446
2014 Crystal structure of MST2 SARAH domain forms antiparallel homodimeric coiled coil; residues critical for MST2 homodimerization also impair its heterodimerization with RASSF5/RAPL SARAH domain; SARAH-mediated homodimerization and heterodimerization with RAPL are both required for full MST2 kinase activation and apoptosis in T cells. X-ray crystallography, structure-guided mutagenesis, kinase activity assay, apoptosis assay in T cells Journal of structural biology High 24468289
2014 RASSF5 acts upstream of Ndr1/Ndr2 kinases in a novel signaling cascade in neurons; Rassf5 and Ndr1/2 are required for hippocampal neuron polarization; Ndr kinases phosphorylate Par3 at Ser383 to inhibit Par3–dynein interaction, thereby polarizing Par3 distribution and specifying a single axon. Neuronal knockdown (shRNA), phosphorylation assay (Ndr→Par3 Ser383), Par3 localization by immunofluorescence, axon specification assay in primary hippocampal neurons Journal of cell science Medium 24928906
2017 In inactive RASSF5, the RA domain retains the SARAH domain in a self-associated autoinhibited conformation (kinked α-helix); K-Ras4B-GTP binding shifts the equilibrium toward SARAH domain interaction with MST kinases, enabling SARAH heterodimerization and MST1/2 kinase domain trans-autophosphorylation; membrane context is required for productive MST activation. All-atom molecular dynamics simulations based on crystal structures of RA and SARAH domains Physical chemistry chemical physics Low 28197608
2019 Histone demethylase Jmjd3 (KDM6B) directly targets the RASSF5 promoter; Jmjd3 knockdown increases H3K27me3 at the RASSF5 promoter and decreases RASSF5 expression, reducing TNF-α-induced osteoblast apoptosis; Jmjd3 thus regulates apoptosis through RASSF5. ChIP assay (H3K27me3 at RASSF5 promoter), shRNA knockdown of Jmjd3, qRT-PCR, apoptosis assays (Annexin V, caspase-3) Connective tissue research Medium 31092054
2021 Engineered high-affinity RASSF5 RA-domain variants, generated by computational design and in vitro evolution, inhibit Ras-regulated pro-cancer pathways and simultaneously stimulate RASSF5 anti-cancer pathways; introduction into A549 cells decreases viability and motility and induces cellular senescence with increased p53 acetylation and decreased p53 phosphorylation, to a greater extent than WT RASSF5. Computational design plus in vitro evolution (phage/yeast display implied), cell viability assay, migration assay, senescence assay, p53 modification Western blot in A549 cells The Journal of biological chemistry Medium 34717958
2023 Irf8 transcriptionally activates RASSF5 (Nore1a) expression during emergency granulopoiesis; Rassf5-knockout mice develop neutrophilia and progress to AML with aging, display sustained emergency granulopoiesis, and show enhanced DNA damage and clonal hematopoiesis in hematopoietic stem cells. Rassf5-knockout mouse model, gene expression analysis, clonal hematopoiesis analysis, Irf8 ChIP/transcription assays The Journal of biological chemistry Medium 37247756

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1. Nature immunology 393 12845325
2004 Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. The Biochemical journal 303 15109305
2006 Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion. Nature immunology 198 16892067
2002 The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Oncogene 188 11857081
1998 Identification of Nore1 as a potential Ras effector. The Journal of biological chemistry 167 9488663
2004 Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking. Nature immunology 151 15361866
2006 Biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase encoded in the rapamycin gene cluster. Journal of the American Chemical Society 106 16536560
2003 The pro-apoptotic Ras effector Nore1 may serve as a Ras-regulated tumor suppressor in the lung. The Journal of biological chemistry 105 12676952
2010 T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes. Immunity 94 20346707
2003 The t(1;3) breakpoint-spanning genes LSAMP and NORE1 are involved in clear cell renal cell carcinomas. Cancer cell 93 14667507
2002 RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1. Oncogene 88 11965544
2013 Structural basis for autoactivation of human Mst2 kinase and its regulation by RASSF5. Structure (London, England : 1993) 82 23972470
2004 Regulation of lymphocyte adhesion and migration by the small GTPase Rap1 and its effector molecule, RAPL. Immunology letters 80 15134891
2004 Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene 74 15007383
1998 Mutational biosynthesis of novel rapamycins by a strain of Streptomyces hygroscopicus NRRL 5491 disrupted in rapL, encoding a putative lysine cyclodeaminase. Journal of bacteriology 74 9473033
2006 Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases. Methods in enzymology 67 16757333
2012 The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. Molecular cancer 64 22695170
2020 Exosomal miR-532-5p from bone marrow mesenchymal stem cells reduce intervertebral disc degeneration by targeting RASSF5. Experimental cell research 63 32464126
2010 Tumor suppressor ras association domain family 5 (RASSF5/NORE1) mediates death receptor ligand-induced apoptosis. The Journal of biological chemistry 63 20810663
2004 Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes. The Journal of biological chemistry 62 15569673
2006 GTP-Ras disrupts the intramolecular complex of C1 and RA domains of Nore1. Structure (London, England : 1993) 58 16698549
2020 In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions. Scientific reports 55 32884013
2018 Autoinhibition in Ras effectors Raf, PI3Kα, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention. Biophysical reviews 43 30269291
2013 The E3 ubiquitin ligase Itch regulates tumor suppressor protein RASSF5/NORE1 stability in an acetylation-dependent manner. Cell death & disease 38 23538446
2011 SKAP1 protein PH domain determines RapL membrane localization and Rap1 protein complex formation for T cell receptor (TCR) activation of LFA-1. The Journal of biological chemistry 35 21669874
2007 Characterization of interactions of adapter protein RAPL/Nore1B with RAP GTPases and their role in T cell migration. The Journal of biological chemistry 33 17716979
2013 Structural and thermodynamic characterization of Nore1-SARAH: a small, helical module important in signal transduction networks. Biochemistry 30 23331050
1995 Classification of multi-helical DNA-binding domains and application to predict the DBD structures of sigma factor, LysR, OmpR/PhoB, CENP-B, Rapl, and Xy1S/Ada/AraC. FEBS letters 30 7556672
2016 RASSF5: An MST activator and tumor suppressor in vivo but opposite in vitro. Current opinion in structural biology 28 27643882
2014 Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway. Journal of cell science 26 24928906
2012 Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1. EMBO reports 24 22173032
2014 RASSF5 inhibits growth and invasion and induces apoptosis in osteosarcoma cells through activation of MST1/LATS1 signaling. Oncology reports 23 25109282
2010 Deficiency of Rap1-binding protein RAPL causes lymphoproliferative disorders through mislocalization of p27kip1. Immunity 23 21194982
2017 The dynamic mechanism of RASSF5 and MST kinase activation by Ras. Physical chemistry chemical physics : PCCP 21 28197608
2010 Epigenetic inactivation of the NORE1 gene correlates with malignant progression of colorectal tumors. BMC cancer 21 20969767
2020 MiR-486-5p-directed MAGI1/Rap1/RASSF5 signaling pathway contributes to hydroquinone-induced inhibition of erythroid differentiation in K562 cells. Toxicology in vitro : an international journal published in association with BIBRA 16 32198055
2018 The Emerging Roles of RASSF5 in Human Malignancy. Anti-cancer agents in medicinal chemistry 16 28356010
2017 MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5. Genetics and molecular research : GMR 14 28290615
2017 TET1 inhibits cell proliferation by inducing RASSF5 expression. Oncotarget 14 29156803
2014 Structure of MST2 SARAH domain provides insights into its interaction with RAPL. Journal of structural biology 14 24468289
2019 Histone demethylase Jmjd3 modulates osteoblast apoptosis induced by tumor necrosis factor-alpha through directly targeting RASSF5. Connective tissue research 8 31092054
2010 Functional interaction of the Ras effector RASSF5 with the tyrosine kinase Lck: critical role in nucleocytoplasmic transport and cell cycle regulation. Journal of molecular biology 7 20064523
2024 Rickettsia rickettsii virulence determinants RARP2 and RapL mitigate IFN-β signaling in primary human dermal microvascular endothelial cells. mBio 6 38445878
2022 Role of MiR-27a-3p in Intervertebral Disc Degeneration through Targeting RASSF5 via MST1/LATS1 and RAS/RAC1 Signaling Pathway. Journal of healthcare engineering 6 35295173
2024 The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis. Stem cells translational medicine 5 38459853
2024 Implications of the SNHG10/miR-665/RASSF5/NF-κB pathway in dihydromyricetin-mediated ischemic stroke protection. PeerJ 4 39726744
2021 Engineered variants of the Ras effector protein RASSF5 (NORE1A) promote anticancer activities in lung adenocarcinoma. The Journal of biological chemistry 3 34717958
2007 Thrombopoietin promotes beta1-integrin-mediated adhesion in hematopoietic cells via the small GTPase Rapl. Experimental hematology 3 17577928
2023 Nore1 inhibits age-associated myeloid lineage skewing and clonal hematopoiesis but facilitates termination of emergency (stress) granulopoiesis. The Journal of biological chemistry 2 37247756
2018 Aberrant RASSF5 gene transcribed region hypermethylation in pediatric hepatoblastomas. International journal of clinical and experimental pathology 2 31949741
2023 PLAGL2 induces nucleus pulposus cell apoptosis via regulating RASSF5 expression and thus accelerates intervertebral disc degeneration. Experimental cell research 1 37364764
2012 Expression, purification, crystallization and preliminary X-ray analysis of the human NORE1 SARAH domain. Acta crystallographica. Section F, Structural biology and crystallization communications 1 22750872
2023 Retracted: Role of MiR-27a-3p in Intervertebral Disc Degeneration through Targeting RASSF5 via MST1/LATS1 and RAS/RAC1 Signaling Pathway. Journal of healthcare engineering 0 37621640

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