Affinage

SOCS6

Suppressor of cytokine signaling 6 · UniProt O14544

Length
535 aa
Mass
59.5 kDa
Annotated
2026-06-10
91 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SOCS6 is a substrate-recruiting adaptor of the elongin BC-based E3 ubiquitin ligase machinery that uses its SH2 domain to capture phosphotyrosine-bearing signaling proteins and its C-terminal SOCS box to drive their ubiquitination and proteasomal degradation, thereby terminating diverse tyrosine-kinase signaling outputs (PMID:12052866, PMID:25172101). Its SH2 domain has a defined phosphopeptide preference (valine at pY+1, hydrophobic residues at pY+2/+3) and directly engages activated receptor tyrosine kinases including c-KIT at pY568 and Flt3 at pY591/pY919, promoting receptor ubiquitination, internalization/turnover, and attenuation of downstream Erk signaling (PMID:12052866, PMID:21030588, PMID:22952242); a 1.45 Å crystal structure of the SH2 domain bound to a c-KIT phosphopeptide defines a high-affinity, BG-loop-mediated interface (PMID:21030588). The same SH2/SOCS-box logic targets the active form of p56lck at the immunological synapse to restrain TCR-driven IL-2 induction (PMID:20007709) and degrades phosphorylated DAB1 in cortical neurons to terminate reelin signaling, with combined Socs6/Socs7 loss recapitulating reelin-deficient cortical layer inversion (PMID:26503265). Beyond its ligase-adaptor role, SOCS6 localizes to both nucleus and cytoplasm and to mitochondria, where it forms a complex with DRP1 and the phosphatase PGAM5, attenuates DRP1 phosphorylation to promote DRP1 mitochondrial translocation, mitochondrial fission, and intrinsic apoptosis (PMID:17603019, PMID:22955947). Through these activities SOCS6 acts broadly as a growth-suppressive and pro-apoptotic factor, and its abundance is set post-transcriptionally by a PKCδ-Erk-dependent stability mechanism and by RNA-level control through m6A demethylation and RNA-binding-protein-mediated mRNA stabilization (PMID:17210122, PMID:22955947, PMID:41644088, PMID:40065730).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Established the core biochemical identity of SOCS6 as an E3 ligase adaptor by showing the SOCS box binds elongins B/C and defining the SH2 phosphopeptide-binding specificity, framing how SOCS6 would later recognize substrates.

    Evidence Phosphopeptide binding specificity assays, Co-IP, and SOCS6 knockout mice

    PMID:12052866

    Open questions at the time
    • Physiological substrates not yet identified
    • No in vivo phenotype linking elongin BC binding to substrate degradation
  2. 2004 High

    Showed SOCS6 is itself an insulin-responsive, proteasome-regulated protein that engages the PI3K regulatory subunit p85, implicating it in metabolic receptor signaling and revealing its own turnover is controlled.

    Evidence Co-IP, SOCS6 transgenic mice, proteasome inhibitor experiments

    PMID:15123678

    Open questions at the time
    • Identity of the ligase degrading SOCS6 not defined
    • Mechanism by which p85 binding improves Akt signaling unresolved
  3. 2006 Medium

    Demonstrated SOCS6 can engage E3 machinery beyond elongin BC (HOIL-1 via its Ubl domain) and that its stability is set by a PKCδ-Erk pathway acting on its N-terminus, establishing multi-ligase engagement and post-translational regulation of SOCS6 levels.

    Evidence Co-IP, ubiquitination and domain-deletion assays; PMA treatment with PKC/Erk inhibitors

    PMID:16643902 PMID:17210122

    Open questions at the time
    • Functional significance of HOIL-1 versus elongin BC engagement unclear
    • Direct PKCδ/Erk target site on SOCS6 not mapped
  4. 2007 Medium

    Defined SOCS6 subcellular distribution (nucleus and cytoplasm) and a domain division of labor in which the N-terminus directs nuclear localization and the C-terminus lowers nuclear Stat3, connecting SOCS6 to JAK-STAT regulation.

    Evidence GFP-tagged localization, domain-deletion constructs, Stat3 western blot

    PMID:17603019

    Open questions at the time
    • Whether Stat3 reduction is via direct ubiquitination not shown
    • Nuclear function of SOCS6 not mechanistically defined
  5. 2009 Medium

    Linked SOCS6 to tumor suppression by showing it is epigenetically silenced in gastric cancer and that restoring it triggers intrinsic apoptosis, providing the first functional growth-suppressive readout.

    Evidence Allelic loss/methylation analysis, ectopic expression, colony formation and mitochondrial membrane potential assays

    PMID:19646809

    Open questions at the time
    • Molecular trigger of apoptosis by SOCS6 not identified at this stage
    • No defined substrate connecting SOCS6 to the apoptotic pathway
  6. 2009 High

    Showed SOCS6 is a negative regulator of T cell activation that selectively binds the active form of p56lck at the immunological synapse to drive its ubiquitination and repress IL-2 induction, providing a complete SH2-to-degradation mechanistic chain for an immune substrate.

    Evidence Yeast two-hybrid, Co-IP, confocal microscopy, ubiquitination and IL-2 reporter assays in Jurkat cells

    PMID:20007709

    Open questions at the time
    • In vivo T cell phenotype not established
    • Whether other TCR-proximal kinases are also targeted unknown
  7. 2010 High

    Provided atomic-resolution proof of substrate recognition by solving the SOCS6 SH2 domain bound to c-KIT pY568 and showing SOCS6 ubiquitinates and turns over c-KIT, cementing the receptor-tyrosine-kinase substrate model.

    Evidence 1.45 Å crystal structure, binding affinity measurement, in vitro ubiquitin ligase and cell-based turnover assays

    PMID:21030588

    Open questions at the time
    • In vivo consequence of c-KIT regulation by SOCS6 not addressed
    • Whether degradation requires the full elongin BC complex in cells not shown structurally
  8. 2012 High

    Extended the RTK-substrate model to Flt3 (binding pY591/pY919, enhancing ubiquitination, internalization and Erk attenuation) and revealed a parallel non-degradative mitochondrial role in which SOCS6/DRP1/PGAM5 complex formation drives fission and intrinsic apoptosis.

    Evidence Phosphopeptide fishing, Co-IP, ubiquitination/internalization assays in Ba/F3 and UT-7 cells; mitochondrial fractionation, DRP1 phosphorylation and apoptosis assays

    PMID:22952242 PMID:22955947

    Open questions at the time
    • How SOCS6 attenuates DRP1 phosphorylation mechanistically (recruitment of PGAM5 vs direct) not fully resolved
    • Relationship between RTK-degradation and mitochondrial functions of SOCS6 unclear
  9. 2017 High

    Established a developmental substrate in vivo by showing Socs6/Socs7 loss phenocopies reelin deficiency through accumulation of phosphorylated DAB1, demonstrating SOCS6 terminates reelin signaling by SH2-mediated DAB1 binding and degradation.

    Evidence Socs6/Socs7 double-knockout mice, genetic epistasis, ex vivo binding and DAB1 mutation analysis, cortical neuron immunostaining

    PMID:26503265

    Open questions at the time
    • Functional redundancy between SOCS6 and SOCS7 not separated
    • Direct demonstration of DAB1 ubiquitination by SOCS6 in vivo not shown
  10. 2018 Medium

    Broadened the tumor-suppressive program by linking SOCS6 to pro-apoptotic and anti-angiogenic transcriptional outputs in prostate cancer, identifying candidate downstream effectors.

    Evidence SOCS6 overexpression, RNA-seq, in vitro and xenograft angiogenesis/apoptosis assays

    PMID:29295692

    Open questions at the time
    • Whether the RNA-seq targets are direct SOCS6 substrates or secondary effects unknown
    • No degradation substrate identified for the anti-angiogenic effect
  11. 2021 Medium

    Connected SOCS6's c-KIT ubiquitination activity to a therapeutic phenotype, showing SOCS6 promotes radiosensitivity and reduces cancer stem cell properties in esophageal carcinoma, while its loss enhances DNA repair and G2/M arrest in a partly p53-dependent manner.

    Evidence Overexpression and knockdown, Co-IP/ubiquitin blotting for c-Kit, clonogenic survival, cell cycle, DNA damage and apoptosis assays, transcriptome sequencing, xenografts

    PMID:33689885 PMID:33712005

    Open questions at the time
    • Direct mechanism linking c-Kit degradation to DNA repair/cell cycle not defined
    • Nature of p53-SOCS6 transcriptional dependence unresolved
  12. 2020 Medium

    Showed the elongin-BC-binding BC-box motif of SOCS6 is sufficient to drive JAK2 ubiquitination and inhibit JAK2-STAT3 signaling, mechanistically tying SOCS6 to STAT pathway suppression and a neuronal differentiation outcome.

    Evidence Intracellular peptide delivery, JAK2 ubiquitination and STAT3 pathway assays, in vivo transplantation

    PMID:32668737

    Open questions at the time
    • Direct binding of full-length SOCS6 to JAK2 not demonstrated
    • Peptide-based readout may not reflect endogenous regulation
  13. 2025 Medium

    Identified new degradation substrates and metabolic outputs, showing SOCS6 ubiquitinates SLC7A11 to drive ferroptosis and suppresses fatty acid synthesis enzymes in ovarian cancer.

    Evidence Overexpression, Co-IP, ubiquitination assay, GSH/ROS/Fe2+ and lipid-enzyme measurements, xenografts

    PMID:41061872

    Open questions at the time
    • Whether SLC7A11 binding is SH2/phosphotyrosine-dependent not addressed
    • Mechanism of FASN/ACC downregulation (direct vs transcriptional) unknown
  14. 2025 Medium

    Resolved upstream RNA-level control of SOCS6, showing m6A demethylation by FTO and lncRNA CASC2/U2AF2-mediated stabilization tune SOCS6 mRNA stability to govern inflammatory and macrophage-polarization outcomes.

    Evidence MeRIP/RIP mapping, FTO and U2AF2 knockdown, mRNA stability assays, exosome transfer, in vivo disease models

    PMID:40065730 PMID:41644088

    Open questions at the time
    • Direct integration of mRNA-level control with SOCS6 protein function not shown
    • Tissue-specificity of these RNA-regulatory axes unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SOCS6 partitions between its E3-adaptor degradation function and its non-degradative mitochondrial fission/apoptosis role, and what governs substrate selection across its many phosphotyrosine targets, remains unresolved.
  • No unifying model coordinating cytoplasmic, nuclear, and mitochondrial SOCS6 pools
  • Substrate hierarchy and context-dependence of SH2-mediated targeting undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005739 mitochondrion 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3
Partners
DAB1DNM1LELOCFLT3KITLCKPGAM5SLC7A11
Complex memberships
Elongin BC E3 ubiquitin ligase complexSOCS6-DRP1-PGAM5 mitochondrial complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 SOCS6 binds to elongins B and C through its SOCS box, consistent with function as an E3 ubiquitin ligase. The SOCS6 SH2 domain preferentially binds phosphopeptides with valine at pY+1 and hydrophobic residues at pY+2 and pY+3. SOCS6 SH2 domain interacts with a protein complex consisting of IRS-4, IRS-2, and the p85 regulatory subunit of PI3-kinase. Biochemical binding assays (phosphopeptide binding specificity), co-immunoprecipitation, and SOCS-6 knockout mice Molecular and cellular biology High 12052866
2004 After insulin stimulation, SOCS6 interacts with the monomeric p85 subunit of class-Ia PI3-kinase but not with p85/p110 dimers, and this interaction improves downstream Akt/PKB signaling. SOCS6 protein is transiently induced by insulin and degraded via a proteasome-mediated mechanism. Co-immunoprecipitation, SOCS6 transgenic mice, proteasome inhibitor experiments, western blot The Journal of biological chemistry High 15123678
2006 The E3 ubiquitin ligase HOIL-1 interacts with SOCS6 through its Ubl domain, requiring the SH2 and SOCS box domains of SOCS6. HOIL-1 stabilizes SOCS6 and induces ubiquitination and degradation of proteins associated with SOCS6, indicating SOCS6 can engage multiple E3 ubiquitin ligase complexes. Co-immunoprecipitation, ubiquitination assays, domain deletion analysis FEBS letters Medium 16643902
2006 SOCS6 protein stability is increased by PMA treatment via a PKCδ-Erk pathway. Both Erk and PKCδ activation are required for increased SOCS6 stability, with Erk acting downstream of PKCδ. Stability depends on the N-terminal region of SOCS6. PMA treatment, pharmacological inhibitors of PKC and Erk, domain deletion analysis, western blot in HEK293T and MCF7 cells Biochemical and biophysical research communications Medium 17210122
2007 Endogenous and overexpressed SOCS6 localizes to both the nucleus and cytoplasm. Nuclear localization requires the N-terminal region (amino acids 1-210). The C-terminal region of SOCS6 is responsible for decreasing Stat3 protein levels in the nucleus. GFP-tagged SOCS6 subcellular localization, domain deletion constructs, western blot for Stat3 protein levels Biochemical and biophysical research communications Medium 17603019
2009 SOCS6 acts as a negative regulator of T cell activation by binding specifically to the active form of p56lck (F505) through its kinase domain. SOCS6 is recruited to the immunological synapse upon APC-T cell conjugation, promotes p56lck ubiquitination and proteasomal targeting, and represses TCR-dependent IL-2 promoter activity. Yeast two-hybrid screening, co-immunoprecipitation, confocal microscopy, ubiquitination assay, IL-2 promoter reporter assay in Jurkat T cells The Journal of biological chemistry High 20007709
2010 The SH2 domain of SOCS6 directly binds c-KIT at phosphotyrosine Y568. Crystal structure (1.45 Å) of SOCS6 SH2 domain bound to c-KIT peptide (residues 564-574) reveals a highly complementary interface with a large BG loop insertion contributing to substrate interaction (Kd = 0.3 μM). SOCS6 has ubiquitin ligase activity toward c-KIT and promotes c-KIT protein turnover in cells. Crystal structure determination (1.45 Å), surface plasmon resonance/binding affinity measurement, in vitro ubiquitin ligase assay, cell-based c-KIT turnover assay The Journal of biological chemistry High 21030588
2012 SOCS6 is targeted to mitochondria, forms a complex with DRP1 and mitochondrial phosphatase PGAM5, attenuates DRP1 phosphorylation, and promotes DRP1 mitochondrial translocation, leading to mitochondrial fission and intrinsic apoptosis. Mutation analyses show SOCS6-mediated apoptosis is coupled to its ability to induce mitochondrial fission. Lentiviral knockdown, co-immunoprecipitation of SOCS6-DRP1-PGAM5 complex, mitochondrial fractionation, DRP1 phosphorylation assays, site-directed mutagenesis, apoptosis assays (Bax conformational change, mitochondrial targeting) Cell death and differentiation High 22955947
2012 SOCS6 directly binds phosphotyrosines 591 and 919 of Flt3 upon ligand stimulation. SOCS6 enhances ubiquitination of Flt3, promotes receptor internalization and degradation, and weakens Erk1/2 (but not Akt) activation. SOCS6 also becomes tyrosine-phosphorylated upon Flt3 stimulation. Phosphopeptide fishing, co-immunoprecipitation, stable Ba/F3 and UT-7 transfectants, ubiquitination assay, receptor internalization/degradation assay, proliferation assay with Flt3-ITD The Journal of biological chemistry High 22952242
2009 SOCS6 is frequently down-regulated in gastric cancer through allelic loss and promoter hypermethylation. Ectopic SOCS6 expression suppresses cell growth and colony formation by activating the intrinsic apoptotic pathway with decreased mitochondrial membrane potential. Allelic loss analysis, methylation-specific PCR, ectopic overexpression, colony formation assay, apoptosis assay, mitochondrial membrane potential measurement Cancer letters Medium 19646809
2014 SOCS6 negatively regulates signaling downstream of multiple receptor tyrosine kinases (including c-KIT and Flt3) primarily through its SH2 domain binding phosphorylated receptor substrates and its SOCS box-mediated ubiquitin ligase activity leading to receptor/substrate degradation. Review/synthesis of prior biochemical and cell-based experiments (Co-IP, ubiquitination assays, cell signaling assays) Tumour biology Medium 25172101
2017 Combined loss of SOCS6 and SOCS7 in mice recapitulates the cortical layer inversion seen in reelin-deficient mice, with dramatic accumulation of the reelin signaling molecule DAB1 in the cortex. The SH2 domains of SOCS6 and SOCS7 bind DAB1 ex vivo; mutation of DAB1 reduces binding and protects from degradation by SOCS6. Phosphorylated DAB1 is elevated in cortical neurons lacking SOCS6 and SOCS7, indicating SOCS6 terminates reelin signaling by promoting DAB1 degradation. SOCS6/SOCS7 double-knockout mice, genetic epistasis, ex vivo binding assays, DAB1 mutation analysis, cortical neuron immunostaining Cerebral cortex High 26503265
2018 SOCS6 promotes apoptosis and inhibits angiogenesis in prostate cancer cells. RNA-sequencing identified Bcl2 and Hspa1a as downstream targets downregulated by SOCS6 overexpression (apoptosis), and F7, Fak3, and Frzb as angiogenesis-related targets suppressed by SOCS6. SOCS6 overexpression, in vitro apoptosis/migration/invasion assays, in vivo xenograft with angiogenesis measurement, next-generation RNA sequencing, pathway enrichment analysis, western blot validation Current cancer drug targets Medium 29295692
2021 SOCS6 promotes radiosensitivity in esophageal squamous cell carcinoma cells and reduces cancer stem cell properties. The mechanism involves ubiquitylation and degradation of c-Kit, confirmed by co-immunoprecipitation and ubiquitin blotting. SOCS6 and c-Kit co-localize in the cytoplasm. SOCS6 overexpression, colony formation assay, flow cytometry (CSC markers), immunofluorescence/confocal co-localization, co-immunoprecipitation, ubiquitin blotting, xenograft mouse model Cancer cell international Medium 33712005
2021 SOCS6 deficiency in esophageal squamous cell carcinoma confers radioresistance by increasing radiation-induced G2/M arrest, enhancing DNA damage repair, and inhibiting radiation-induced apoptosis. Transcriptome sequencing shows SOCS6 transcription is partially p53-dependent. SOCS6 knockdown (RNAi), clonogenic survival assay, cell cycle analysis, DNA damage repair assays, apoptosis assay, transcriptome sequencing, in vivo xenograft irradiation model Biochemical and biophysical research communications Medium 33689885
2020 BC-box motif in SOCS6 (SLQYLCRFVI, the elongin BC binding site) mediates neuronal differentiation of somatic stem cells. Peptide delivery of the BC-box motif induces GABAergic neuronal differentiation via ubiquitination of JAK2 and inhibition of the JAK2-STAT3 pathway. Intracellular peptide delivery, neuronal differentiation assays (GABA marker expression), JAK2 ubiquitination assay, STAT3 pathway analysis, in vivo transplantation into ischemic rodent model International journal of molecular sciences Medium 32668737
2025 SOCS6 promotes ubiquitin-proteasomal degradation of SLC7A11 (the cystine/glutamate transporter xCT), reducing intracellular glutathione and increasing ROS and Fe2+ accumulation to drive ferroptosis in ovarian cancer cells. SOCS6 also suppresses de novo fatty acid synthesis by downregulating FASN and ACC. SOCS6 overexpression, co-immunoprecipitation, ubiquitination assay, ferroptosis induction (erastin), GSH/ROS/Fe2+ measurement, western blot for lipid metabolism enzymes, xenograft mouse model Gene Medium 41061872
2025 FTO (m6A demethylase) selectively binds and demethylates N6-methyladenosine modifications within the coding sequence of SOCS6 mRNA in keratinocytes, reducing SOCS6 mRNA stability and protein expression, which activates inflammatory programs. IL-1β, S100A8, and S100A9 are downstream effectors of this FTO/SOCS6-m6A axis. Transcriptomic and epitranscriptomic (m6A) sequencing, RNA immunoprecipitation (RIP), MeRIP to map m6A on SOCS6 mRNA, FTO knockdown in vivo and in vitro, mRNA stability assays, western blot The Journal of investigative dermatology Medium 41644088
2025 lncRNA CASC2 stabilizes SOCS6 mRNA by recruiting the RNA-binding protein U2AF2. This CASC2/U2AF2/SOCS6 axis in retinal pigment epithelium-derived exosomes inhibits M1 macrophage polarization and promotes M2 polarization in diabetic retinopathy. RNA immunoprecipitation (RIP), dual-luciferase reporter assay, U2AF2 knockdown, mRNA stability assay, exosome isolation/transfer, macrophage polarization flow cytometry, in vivo diabetic rat model Diabetic medicine Medium 40065730
2014 SOCS6 silencing (via miR-494-3p overexpression) activates STAT3 signaling and promotes megakaryocyte differentiation of hematopoietic stem/progenitor cells. SOCS6 was confirmed as a direct miR-494-3p target by luciferase assay; SOCS6 silencing alone mimics the megakaryocyte hyperplasia phenotype of primary myelofibrosis. miRNA overexpression in CD34+ HSPCs, gene expression profiling, luciferase reporter assay, western blot for SOCS6 and STAT3, megakaryocyte differentiation assays, miR-494-3p inhibition in PMF HSPCs Oncotarget Medium 28423484

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN. Oncotarget 159 27811366
2002 SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. Molecular and cellular biology 126 12052866
2015 MiRNA-155 mediates TAM resistance by modulating SOCS6-STAT3 signalling pathway in breast cancer. American journal of translational research 89 26692956
2013 MicroRNA-424-5p suppresses the expression of SOCS6 in pancreatic cancer. Pathology oncology research : POR 89 23653113
2006 The novel gamma secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse. The Journal of pharmacology and experimental therapeutics 71 17099072
2014 miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells. FEBS letters 67 24801601
2012 Suppressor of cytokine signaling 6 (SOCS6) promotes mitochondrial fission via regulating DRP1 translocation. Cell death and differentiation 65 22955947
2012 Suppressor of cytokine signaling 6 (SOCS6) negatively regulates Flt3 signal transduction through direct binding to phosphorylated tyrosines 591 and 919 of Flt3. The Journal of biological chemistry 63 22952242
2009 SOCS6, down-regulated in gastric cancer, inhibits cell proliferation and colony formation. Cancer letters 61 19646809
2014 Identification of SOCS2 and SOCS6 as biomarkers in human colorectal cancer. British journal of cancer 59 25025962
2010 Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase. The Journal of biological chemistry 58 21030588
2004 Insulin induces SOCS-6 expression and its binding to the p85 monomer of phosphoinositide 3-kinase, resulting in improvement in glucose metabolism. The Journal of biological chemistry 56 15123678
2019 Abnormal expression of long noncoding RNA FGD5-AS1 affects the development of periodontitis through regulating miR-142-3p/SOCS6/NF-κB pathway. Artificial cells, nanomedicine, and biotechnology 54 31144533
2015 MiR-21 and miR-183 can simultaneously target SOCS6 and modulate growth and invasion of hepatocellular carcinoma (HCC) cells. European review for medical and pharmacological sciences 49 26400524
2006 In vivo characterization of Abeta(40) changes in brain and cerebrospinal fluid using the novel gamma-secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) in the rat. The Journal of pharmacology and experimental therapeutics 49 16443723
2020 miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6. Oxidative medicine and cellular longevity 48 32587662
2015 MiR-301a promotes colorectal cancer cell growth and invasion by directly targeting SOCS6. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 48 25591765
1995 (+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7- bc][2,6]-naphthyridine: a 5-HT2C/2B receptor antagonist with low 5-HT2A receptor affinity. Journal of medicinal chemistry 43 7837236
2014 SOCS6 is a selective suppressor of receptor tyrosine kinase signaling. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 25172101
2007 The skeletal rearrangement of gold- and platinum-catalyzed cycloisomerization of cis-4,6-dien-1-yn-3-ols: pinacol rearrangement and formation of bicyclo[4.1.0]heptenone and reorganized styrene derivatives. Journal of the American Chemical Society 41 18020448
2019 miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC. Cell death & disease 39 30737371
2018 Long noncoding RNA neuroblastoma-associated transcript 1 gene inhibits malignant cellular phenotypes of bladder cancer through miR-21/SOCS6 axis. Cell death & disease 39 30310053
2008 Cation diffusion facilitator Cis4 is implicated in Golgi membrane trafficking via regulating zinc homeostasis in fission yeast. Molecular biology of the cell 38 18199682
2007 The nuclear localization of SOCS6 requires the N-terminal region and negatively regulates Stat3 protein levels. Biochemical and biophysical research communications 38 17603019
2020 Regulation of the miR-19b-mediated SOCS6-JAK2/STAT3 pathway by lncRNA MEG3 is involved in high glucose-induced apoptosis in hRMECs. Bioscience reports 37 32519748
2014 Downregulation of microRNA-431 by human interferon-β inhibits viability of medulloblastoma and glioblastoma cells via upregulation of SOCS6. International journal of oncology 36 24584142
2015 MiR-142-3p Suppresses SOCS6 Expression and Promotes Cell Proliferation in Nasopharyngeal Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 26183850
2016 MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1α feedback loop. European review for medical and pharmacological sciences 34 27249600
2021 Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6. Cell death & disease 31 33589592
2006 The E3 ubiquitin ligase HOIL-1 induces the polyubiquitination and degradation of SOCS6 associated proteins. FEBS letters 31 16643902
2018 gga-miR-454 suppresses infectious bursal disease virus (IBDV) replication via directly targeting IBDV genomic segment B and cellular Suppressors of Cytokine Signaling 6 (SOCS6). Virus research 30 29777734
2009 SOCS-6 negatively regulates T cell activation through targeting p56lck to proteasomal degradation. The Journal of biological chemistry 30 20007709
2017 miR-19 promotes osteosarcoma progression by targeting SOCS6. Biochemical and biophysical research communications 28 28986253
2011 SOCS5 and SOCS6 have similar expression patterns in normal and cancer tissues. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 28 22081311
2018 SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer. Current cancer drug targets 26 29295692
2021 MicroRNA-653-5p Promotes Gastric Cancer Proliferation and Metastasis by Targeting the SOCS6-STAT3 Pathway. Frontiers in molecular biosciences 25 33937336
2021 Inhibition of miR-1298-5p attenuates sepsis lung injury by targeting SOCS6. Molecular and cellular biochemistry 25 34100174
2017 miR-494 inhibits cervical cancer cell proliferation through upregulation of SOCS6 expression. Oncology letters 24 29456720
2014 SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells. International journal of molecular medicine 23 24626642
2023 Extracellular vesicle-encapsulated microRNA-296-3p from cancer-associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways. Cancer science 22 37972389
2001 Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 21 11337571
2021 Circ_0085289 Alleviates the Progression of Periodontitis by Regulating let-7f-5p/SOCS6 Pathway. Inflammation 20 33710445
2021 SOCS6 promotes radiosensitivity and decreases cancer cell stemness in esophageal squamous cell carcinoma by regulating c-Kit ubiquitylation. Cancer cell international 20 33712005
2003 Synthesis, resolution, and determination of the absolute configuration of the enantiomers of cis-4,5-dihydroxy-1,2-dithiane 1,1-dioxide, an HIV-1NCp7 inhibitor. Bioorganic & medicinal chemistry 18 12818684
2022 LncRNA FLG-AS1 Mitigates Diabetic Retinopathy by Regulating Retinal Epithelial Cell Inflammation, Oxidative Stress, and Apoptosis via miR-380-3p/SOCS6 Axis. Inflammation 17 35461393
2018 Interference with NTSR1 Expression Exerts an Anti-Invasion Effect via the Jun/miR-494/SOCS6 Axis of Glioblastoma Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 16 30261490
2017 Cortical Layer Inversion and Deregulation of Reelin Signaling in the Absence of SOCS6 and SOCS7. Cerebral cortex (New York, N.Y. : 1991) 16 26503265
2017 The involvement of suppressor of cytokine signaling 6 (SOCS6) in immune response of Chinese mitten crab Eriocheir sinensis. Fish & shellfish immunology 16 29155031
2023 Exosome-mediated long noncoding RNA (lncRNA) PART1 suppresses malignant progression of oral squamous cell carcinoma via miR-17-5p/SOCS6 axis. Turkish journal of medical sciences 14 37476905
2017 miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis hematopoietic stem/progenitor cells by targeting SOCS6. Oncotarget 14 28423484
2006 Increased SOCS6 stability with PMA requires its N-terminal region and the Erk pathway via Pkcdelta activation. Biochemical and biophysical research communications 14 17210122
2022 SOCS6 Promotes Mitochondrial Fission and Cardiomyocyte Apoptosis and Is Negatively Regulated by Quaking-Mediated miR-19b. Oxidative medicine and cellular longevity 13 35126805
2022 Methyltransferase-like 3 facilitates lung cancer progression by accelerating m6A methylation-mediated primary miR-663 processing and impeding SOCS6 expression. Journal of cancer research and clinical oncology 13 35907010
2021 Circular RNA _0015278 inhibits the progression of non-small cell lung cancer through regulating the microRNA 1278/SOCS6 gene axis. Annals of translational medicine 12 34532392
2019 kshv-mir-k12-1-5p promotes cell growth and metastasis by targeting SOCS6 in Kaposi's sarcoma cells. Cancer management and research 12 31213914
1983 In vivo effects of cis-5,8,11,14,17-20:5 (n-3) and cis-4,7,10,13,16,19-22:6(n-3) on serum lipoproteins, platelet aggregation, and lipid metabolism in the aorta of rats. The Tohoku journal of experimental medicine 12 6322383
2022 MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment. Kidney & blood pressure research 11 35038704
2022 Circ_0062491 alleviates LPS-induced apoptosis and inflammation in periodontitis by regulating miR-498/SOCS6 axis. Innate immunity 11 35678490
2020 microRNA-454 promotes liver tumor-initiating cell expansion by regulating SOCS6. Experimental cell research 11 32165166
2020 cis-4-[18F]fluoro-L-proline Molecular Imaging Experimental Liver Fibrosis. Frontiers in molecular biosciences 10 32500081
2019 Molecular Cloning and Expression Analysis of Three Suppressors of Cytokine Signaling Genes (SOCS5, SOCS6, SOCS7) in the Mealworm Beetle Tenebrio molitor. Insects 10 30884777
2023 Protective mechanism of gold nanoparticles on human neural stem cells injured by β-amyloid protein through miR-21-5p/SOCS6 pathway. Neurotoxicology 9 36623431
2012 Studies on the roles of clathrin-mediated membrane trafficking and zinc transporter Cis4 in the transport of GPI-anchored proteins in fission yeast. PloS one 9 22848669
2022 MIP From Legionella pneumophila Influences the Phagocytosis and Chemotaxis of RAW264.7 Macrophages by Regulating the lncRNA GAS5/miR-21/SOCS6 Axis. Frontiers in cellular and infection microbiology 8 35573783
2020 BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons. International journal of molecular sciences 8 32668737
2022 HnRNPU-AS1 inhibits the proliferation, migration and invasion of HCC cells and induces autophagy through miR-556-3p/ miR-580-3p/SOCS6 axis. Cancer biomarkers : section A of Disease markers 7 35275521
2020 Correction: miR-1260b, mediated by YY1, activates KIT signaling by targeting SOCS6 to regulate cell proliferation and apoptosis in NSCLC. Cell death & disease 7 32317628
2017 Expression of SHP-1 and SOCS6 in patients with acute leukemia and their clinical implication. OncoTargets and therapy 7 28408843
2009 Synthesis of trans- and cis-4'-hydroxylomustine and development of validated analytical method for lomustine and trans- and cis-4'-hydroxylomustine in canine plasma. Journal of analytical toxicology 7 20040134
1999 Ab Initio Study of Intramolecular Ring Cyclization of Protonated and BF(3)-Coordinated trans- and cis-4,5-Epoxyhexan-1-ol. The Journal of organic chemistry 6 11674617
2025 MiR-203 improved renal cell injury in diabetic nephropathy by targeting SOCS6/SOCS7 and inhibiting JAK/STAT pathway activation. Scientific reports 5 40155732
2022 Conformational flexibility enables catalysis of phthalate cis-4,5-dihydrodiol dehydrogenase. Archives of biochemistry and biophysics 5 35667443
2021 Inhibition of SOCS6 confers radioresistance in esophageal squamous cell carcinoma. Biochemical and biophysical research communications 5 33689885
2016 A validated, sensitive HPLC-MS/MS method for quantification of cis-para-methyl-4-methylaminorex (cis-4,4'-DMAR) in rat and human plasma: application to pharmacokinetic studies in rats. Drug testing and analysis 5 27509066
2022 Genotoxicological Characterization of (±)cis-4,4'-DMAR and (±)trans-4,4'-DMAR and Their Association. International journal of molecular sciences 4 35628658
2021 Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice. International journal of molecular sciences 4 34445476
2018 Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment. Molecular imaging and biology 4 29687323
2025 LncRNA CASC2 mediates SOCS6 mRNA stabilization via U2AF2 recruitment to modulate macrophage polarisation in diabetic retinopathy. Diabetic medicine : a journal of the British Diabetic Association 2 40065730
2025 Dual-Mode Radiosensitization of Esophageal Squamous Cell Carcinoma via SOCS6-Loaded Virus-Inspired Manganese-Bismuth Bimetallic Oxide Nanoparticles. Advanced healthcare materials 2 40159874
2024 SOCS6, an inhibitory factor in Japanese eel inhibits the type I IFN pathway and the MyD88-mediated NF-kB pathway. Fish & shellfish immunology 2 39276815
2023 Radiosynthesis and Preliminary Evaluation of [11C]SSI-4 for the Positron Emission Tomography Imaging of Stearoyl CoA Desaturase 1. Molecular pharmaceutics 2 37409698
2023 Evaluation of trans- and cis-4-[18F]Fluorogabapentin for Brain PET Imaging. ACS chemical neuroscience 2 37947793
2025 Suppressor of cytokine signaling 6 (SOCS6) mediates ubiquitination degradation of SLC7A11 to drive ferroptosis and block lipid metabolism in ovarian cancer cells. Gene 1 41061872
2025 [Expression and clinical significance of SIRT1 and SOCS6 in gingival tissue of patients with severe chronic periodontitis]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 1 41311181
2022 Cis-4-[18F]fluoro-L-proline PET/CT molecular imaging quantifying liver collagenogenesis: No existing fibrotic deposition in experimental advanced-stage alcoholic liver fibrosis. Frontiers in nuclear medicine 1 39354960
2026 FTO/SOCS6-m6A axis epigenetic modification links obesity to atopic dermatitis by regulating keratinocyte function. The Journal of investigative dermatology 0 41644088
2026 Excited-state-dependent chiral pathways in the photoisomerization of cis-4,4'-azopyridine. The Journal of chemical physics 0 41919701
2025 Association of SOCS6 Gene Polymorphisms and Promoter Hypermethylation With the Progression of Hepatitis B Virus Infection. International journal of immunogenetics 0 41174995
2023 Serum levels of SOCS6 are decreased in diabetic retinopathy and are related to severity of the disease. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 0 37589228
2023 Quantification Of Collagenogenesis In Experimental Early-stage Alcoholic Liver Fibrosis Using Cis-4-[18F]fluoro-L-Proline microPET. Current medical imaging 0 37622557
2023 Evaluation of trans- and cis-4-[18F]fluorogabapentin for brain PET imaging. bioRxiv : the preprint server for biology 0 37732236

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