Affinage

SOCS1

Suppressor of cytokine signaling 1 · UniProt O15524

Length
211 aa
Mass
23.6 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 29 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

SOCS1 is a cytokine-inducible negative-feedback regulator of JAK-STAT signaling that operates as both a direct kinase inhibitor and a substrate-recruiting component of an E3 ubiquitin ligase (PMID:10064597, PMID:9789053, PMID:9716595). Its core inhibitory mechanism couples an extended SH2 domain, which binds the phosphorylated activation-loop tyrosine (Y1007) of JAK2, to an adjacent kinase inhibitory region (KIR) that occupies the substrate-binding groove of the JAK catalytic domain to block phosphorylation (PMID:10064597, PMID:29674694). Strongly induced by IFN-γ, SOCS1 thereby suppresses JAK1/JAK2 activation, STAT1 tyrosine phosphorylation, and the antiviral response (PMID:9716595), and analogous inhibition extends to JAK3/IL-2Rβ-driven STAT5 signaling (PMID:11133764). In parallel, SOCS1 functions as an adaptor of a Cullin-Elongin BC E3 ligase: its SOCS box engages Elongin B/C and Cullin-2, while the SH2 domain selects substrates for K48-linked ubiquitination and proteasomal degradation, including IRS1/IRS2, the leukemic fusion TEL-JAK2, and the GM-CSF receptor βc subunit (PMID:12228220, PMID:11278610, PMID:24086733). Beyond cytokine signaling, SOCS1 acts as a tumor suppressor by binding the p53 transactivation domain through its SH2 domain and engaging ATM/ATR through its SOCS box to drive p53 phosphorylation, transcriptional activity, and senescence, and it also directs K63-ubiquitylation of VHL to support DNA double-strand-break repair (PMID:20005840, PMID:23455319). SOCS1 abundance and activity are tightly tuned post-transcriptionally: SOCS box-Elongin BC engagement stabilizes the protein (PMID:9789053, PMID:11522790), translation is repressed by upstream AUGs in its 5'UTR (PMID:10764816), and turnover is linked to MTOC-associated 20S proteasome localization via the SH2 domain (PMID:15456882). Pim kinases phosphorylate and stabilize SOCS1 to potentiate STAT inhibition (PMID:11854514), whereas SRC-family phosphorylation of Y80 blocks the p53 interaction and drives cytoplasmic sequestration, and Bcr-Abl phosphorylation of Y155/Y204 inactivates JAK/STAT inhibition to promote transformation (PMID:31101761, PMID:22787435). Heterozygous germline loss-of-function mutations in SOCS1 cause an autoimmune/inflammatory disorder of JAK-STAT hyperactivation reversible by ruxolitinib (PMID:33087723).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Established the molecular basis of JAK inhibition: how SOCS1 recognizes an active kinase and shuts it off.

    Evidence In vitro binding and kinase assays with site-directed mutagenesis mapping SH2/extended-SH2 and KIR contacts on JAK2 Y1007

    PMID:10064597

    Open questions at the time
    • Inhibition demonstrated for JAK2; specificity across all JAK family members not fully resolved in this study
    • No high-resolution co-structure provided at this stage
  2. 1998 High

    Defined the modular domain architecture (pre-SH2, SH2, SOCS box) required for cytokine suppression and protein stability, clarifying division of labor within SOCS1.

    Evidence Deletion mutagenesis with co-IP, reporter assays, and proteasome inhibition in the IL-6 system

    PMID:9789053

    Open questions at the time
    • SOCS box partner identity (Elongin BC) inferred, not yet biochemically defined here
    • Did not resolve which JAK is the principal physiological target
  3. 1998 High

    Connected SOCS1 to a physiological feedback loop, showing IFN-induced SOCS1 confers cytokine/antiviral resistance via JAK-STAT1 blockade.

    Evidence Stable overexpression with kinase, STAT1 phosphorylation/DNA-binding, and antiviral assays

    PMID:9716595

    Open questions at the time
    • Constitutive SOCS1 in IFN-resistant tumors observational, not causally tested
    • Endogenous induction kinetics not dissected
  4. 2001 High

    Revealed SOCS1 is not only a kinase blocker but an E3 ligase adaptor, recruiting Cullin-2/Elongin BC to ubiquitinate and degrade phosphorylated JAK substrates.

    Evidence Ubiquitination assays, dominant-negative Cullin-2 rescue, and proteasome inhibition on TEL-JAK2

    PMID:11278610

    Open questions at the time
    • Demonstrated on a leukemic fusion; degradation of native full-length JAK2 generality not fully established
    • Stoichiometry and chain linkage not characterized
  5. 2002 High

    Extended the ligase mechanism to metabolic signaling, showing SOCS1 targets IRS1/IRS2 for degradation with in vivo physiological consequence.

    Evidence Co-IP, ubiquitination assays, SOCS box mutagenesis, and adenoviral SOCS1 expression in mouse liver with glucose tolerance testing

    PMID:12228220

    Open questions at the time
    • Adenoviral overexpression may exceed physiological levels
    • Did not separate degradation from kinase-inhibitory contributions to glucose intolerance
  6. 2002 High

    Placed SOCS1 in innate immune feedback, demonstrating it restrains LPS-driven NF-κB/STAT1 activation and is required for endotoxin tolerance.

    Evidence SOCS1 knockout mice, macrophage stimulation, and forced expression with NF-κB/STAT1 readouts

    PMID:12433365 PMID:12433373

    Open questions at the time
    • Direct molecular target on the TLR4 pathway not defined here
    • NF-κB regulation later found cell-type dependent
  7. 2002 High

    Identified Pim kinases as positive regulators that phosphorylate and stabilize SOCS1, defining a kinase-controlled input to feedback strength.

    Evidence Co-IP, phosphorylation/stability assays, and Pim-1/Pim-2 double-knockout mice with STAT6 readout

    PMID:11854514

    Open questions at the time
    • Phosphosites on SOCS1 not mapped here
    • Mechanism linking phosphorylation to stabilization inferred
  8. 2004 High

    Defined the cellular geography of SOCS1 turnover, localizing it to the MTOC-associated 20S proteasome via its SH2 domain.

    Evidence Immunofluorescence colocalization, co-purification, SH2 deletion, and nocodazole perturbation in SOCS1-deficient cells

    PMID:15456882

    Open questions at the time
    • Functional necessity of MTOC localization for substrate degradation not established
    • Transport machinery for minus-end delivery not identified
  9. 2009 High

    Uncovered a tumor-suppressor mechanism distinct from cytokine signaling: SOCS1 directly engages p53 and ATM/ATR to drive p53 activation and senescence.

    Evidence Reciprocal co-IP, DNA-damage foci colocalization, p53 reporter assays, and loss/gain-of-function in fibroblasts

    PMID:20005840

    Open questions at the time
    • Whether SOCS1 ligase activity acts on p53/ATM substrates not resolved here
    • Link to STAT5 context-dependency incompletely mapped
  10. 2012 High

    Showed oncogenic kinases can inactivate SOCS1, with Bcr-Abl phosphorylating Y155/Y204 to disable JAK/STAT inhibition and enable transformation.

    Evidence Mass spectrometry, mutagenesis, co-IP, STAT5/JAK assays, and in vivo tumorigenesis/bone marrow transformation

    PMID:22787435

    Open questions at the time
    • Structural basis of how Y155/Y204 phosphorylation disrupts KIR/SH2 function not defined
    • Contribution of degradation versus kinase inhibition to the rescued phenotype unclear
  11. 2013 Medium

    Expanded the ligase output to the DNA-damage response, showing SOCS1 directs K63-ubiquitylation and nuclear redistribution of VHL to support homologous recombination.

    Evidence K63-specific ubiquitylation assays, localization, VHL mutant analysis, and DNA repair readouts

    PMID:23455319

    Open questions at the time
    • Single lab; reciprocal validation limited
    • How SOCS1 switches from K48-degradative to K63-signaling ubiquitination not explained
  12. 2017 High

    Linked SOCS1's KIR-dependent activity to control of macrophage metabolic reprogramming via the STAT3/HIF-1α/glycolysis axis during sepsis.

    Evidence Myeloid-specific SOCS1 knockout, CLP sepsis model, metabolic measurements, and KIR-blocking peptide (iKIR)

    PMID:28679957

    Open questions at the time
    • Direct kinase target driving STAT3/HIF-1α not pinpointed
    • Whether ligase activity contributes alongside KIR not tested
  13. 2019 High

    Defined a switch governing SOCS1's tumor-suppressor arm: SRC-family phosphorylation of Y80 blocks p53 binding and drives cytoplasmic SOCS1 in lymphoma.

    Evidence Mass spectrometry, Y80E phosphomimetic mutagenesis, kinase library screen, co-IP, senescence assays, and IHC

    PMID:31101761

    Open questions at the time
    • Whether Y80 phosphorylation also alters JAK inhibition not addressed
    • Reversibility/phosphatase regulation of Y80 not defined
  14. 2020 High

    Established human disease relevance: SOCS1 haploinsufficiency causes JAK-STAT hyperactivation reversible by JAK inhibition.

    Evidence Exome/genome sequencing of patients, lymphocyte STAT phosphorylation assays, and ruxolitinib rescue

    PMID:33087723

    Open questions at the time
    • Genotype-phenotype variability across families not fully explained
    • Which downstream STAT dominates pathology not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SOCS1 partitions between its kinase-inhibitory, K48-degradative, and K63-signaling/p53 tumor-suppressor functions in a given cell, and what dictates substrate and ubiquitin-linkage choice, remains unresolved.
  • No unified model integrating direct inhibition versus ligase versus p53 functions
  • Regulation of ubiquitin chain-type choice (K48 vs K63) unknown
  • In vivo balance of these arms across tissues not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-73894 DNA Repair 1
Partners
CULLIN-2ELONGIN B/CJAK1JAK2PIM-1TP53TYK2VHL
Complex memberships
Elongin BC-Cullin-2 E3 ubiquitin ligaseMTOC-associated 20S proteasome

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SOCS1/JAB binds specifically to the phosphorylated tyrosine residue Y1007 in the activation loop of JAK2, requiring both the SH2 domain and an N-terminal extended SH2 subdomain (containing Ile68 and Leu75). An additional kinase inhibitory region (KIR) contributes to high-affinity binding to the JAK2 kinase domain and is required for inhibition of JAK2 signaling and kinase activity. In vitro binding assays, site-directed mutagenesis, kinase activity assays The EMBO journal High 10064597
2018 Crystal/structural studies revealed that the SOCS1 kinase inhibitory region (KIR) targets the substrate-binding groove of JAK with high specificity to block phosphorylation. SOCS1 has a compromised ability to recruit Cullin5 due to alterations within its SOCS box domain, making direct JAK catalytic inhibition its primary mode of action. SOCS1 does not bind the IFNγ receptor, distinguishing its mechanism from SOCS3. Structural determination (crystallography/biophysical), in vitro kinase assays, mutagenesis Nature communications High 29674694
1998 Three distinct domains of SOCS1/SSI-1 are required for suppression of IL-6 signaling: (1) the pre-SH2 domain (24 aa N-terminal to the SH2 domain), (2) the SH2 domain (required for association with JAK family kinases including JAK1, JAK2, TYK2), and (3) the SC-motif (SOCS box), which protects SOCS1 from proteasomal degradation. Deletion of the SH2 domain abolished co-association with TYK2. Deletion mutagenesis, co-expression/co-immunoprecipitation, reporter assays, proteasome inhibitor treatment Proceedings of the National Academy of Sciences of the United States of America High 9789053
2002 SOCS1 and SOCS3 bind both recombinant and endogenous IRS1 and IRS2, promote their ubiquitination and subsequent proteasomal degradation. Mutations in the conserved SOCS box of SOCS1 abrogated interaction with the elongin BC ubiquitin-ligase complex without affecting IRS1/IRS2 binding, and abolished ubiquitination and degradation. Adenoviral expression of SOCS1 in mouse liver dramatically reduced hepatic IRS1 and IRS2 protein levels and caused glucose intolerance. Co-immunoprecipitation, ubiquitination assays, SOCS box mutagenesis, adenoviral gene delivery in mice, glucose tolerance testing The Journal of biological chemistry High 12228220
2001 The SOCS box of SOCS1 interacts with Cullin-2 (in addition to Elongin B/C) and promotes ubiquitination of the leukemic fusion protein TEL-JAK2, leading to its proteasomal degradation. Dominant-negative Cullin-2 suppressed SOCS1-dependent TEL-JAK2 degradation. Degradation required JAK2 phosphorylation and high-affinity binding through the KIR and SH2 domain of SOCS1. Co-immunoprecipitation, ubiquitination assays, dominant-negative Cullin-2 overexpression, proteasome inhibitor experiments The Journal of biological chemistry High 11278610
1998 JAB/SOCS1 is strongly induced by IFN-γ; forced expression of JAB confers resistance to IFN-β and IFN-γ by inhibiting JAK1 and JAK2 activation and blocking STAT1 tyrosine phosphorylation and DNA-binding activity. IFN-resistant tumor cell clones expressed high constitutive levels of JAB. Stable cell line overexpression, antiviral assay, kinase activity assay, STAT1 phosphorylation and DNA-binding assays Blood High 9716595
2002 SOCS1 expression is rapidly induced in macrophages by LPS. SOCS1 deficiency increases sensitivity to LPS-induced shock and augments inflammatory cytokine production. Forced SOCS1 expression inhibits LPS-induced NF-κB and STAT1 activation. SOCS1-deficient mice fail to develop LPS tolerance. SOCS1 knockout mice, macrophage stimulation assays, NF-κB and STAT1 reporter/phosphorylation assays, forced SOCS1 expression Immunity High 12433365 12433373
2009 SOCS1 is required for p53 transcriptional activity, DNA binding, and serine-15 phosphorylation in the context of STAT5 signaling. SOCS1 directly interacts with p53 via its SH2 domain (binding the N-terminal transactivation domain of p53), while the SOCS box mediates interaction with DNA damage kinases ATM/ATR. SOCS1 colocalizes with ATM at DNA damage foci. SOCS1 is sufficient to induce p53-dependent senescence in fibroblasts. Co-immunoprecipitation, immunofluorescence co-localization, p53 activity reporter assays, SOCS1 KO cells, overexpression in fibroblasts Molecular cell High 20005840
2002 TRIM8/GERP, a RING finger protein, interacts with SOCS1 in vitro and in vivo. Coexpression of TRIM8/GERP with SOCS1 decreases SOCS1 protein stability and levels, and functionally decreases SOCS1-mediated repression of IFN-γ signaling. Co-immunoprecipitation, protein stability assays, IFN-γ signaling reporter assays The Journal of biological chemistry Medium 12163497
2002 Pim serine/threonine kinases interact with SOCS1 in thymocytes; coexpression results in phosphorylation and stabilization of SOCS1 protein. Pim-1/Pim-2 double-knockout mice have significantly reduced SOCS1 protein levels and show prolonged STAT6 phosphorylation upon IL-4 stimulation. Co-immunoprecipitation, protein stability/phosphorylation assays, Pim-1/Pim-2 double-knockout mouse analysis, STAT6 phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America High 11854514
2004 Pim-1 kinase interacts with SOCS1 and SOCS3 and potentiates their inhibitory effects on STAT5, most likely via phosphorylation-mediated stabilization of SOCS proteins. Pim-1 reduced tyrosine phosphorylation and DNA binding of STAT5 in cytokine-responsive cells without directly phosphorylating or binding STAT5. Co-immunoprecipitation, STAT5 phosphorylation assays, STAT5 DNA-binding assays, ectopic Pim-1 expression Blood Medium 14764533
2001 SOCS1/JAB associates with both JAK1 and JAK3 in cotransfection experiments, as well as with IL-2Rβ through the A region (residues 313-382). SOCS1 overexpression strongly inhibits IL-2-induced STAT5 phosphorylation and transcriptional activity, with greater effect on JAK1 than JAK3. The IL-2Rβ interaction was not essential for inhibitory action. Co-immunoprecipitation, STAT5 phosphorylation assays, transcriptional activity assays, deletion mutants Blood Medium 11133764
1997 SOCS1/JAB/SSI-1 (identified as TIP3) associates with Tec tyrosine kinase in 293 cells and suppresses its kinase activity, as well as down-regulating JAK2 activity. SOCS1 did not downregulate Lyn kinase activity, demonstrating substrate selectivity. Yeast two-hybrid screen, co-immunoprecipitation in 293 cells, in vitro kinase assays The Journal of biological chemistry Medium 9341160
2004 SOCS1 localizes to the microtubule organizing complex (MTOC) and co-purifies with the MTOC-associated 20S proteasome; this localization requires the SH2 domain of SOCS1. Overexpression of SOCS1 targets JAK1 to a perinuclear distribution resembling the MTOC-associated proteasome. Nocodazole (microtubule depolymerization) inhibits SOCS1 protein turnover, indicating that minus-end transport to the MTOC-associated proteasome regulates SOCS1 levels. Immunofluorescence colocalization, biochemical co-purification, SH2 domain deletion mutants, nocodazole treatment, fractionation from SOCS1-deficient cells Molecular and cellular biology High 15456882
2000 SOCS1 expression is repressed at the level of translation initiation by the 5' untranslated region, mediated by two upstream AUGs. SOCS1 translation is cap-dependent and modulated by eIF4E-binding proteins. 5'UTR deletion/mutation constructs, translation reporter assays, eIF4E-binding protein manipulation The Journal of biological chemistry Medium 10764816
2000 SOCS1 can suppress CD3ζ- and Syk-mediated NF-AT activation in non-lymphoid cells by interacting with Syk and with immunoreceptor tyrosine-based activation motifs (ITAMs) in CD3ζ. Cotransfection in 293T cells, NF-AT reporter assays, co-immunoprecipitation FEBS letters Medium 10788618
2001 A dominant-negative SOCS1 mutant (F59D-JAB) sustained JAK/STAT activation by chelating the Elongin BC complex, thereby destabilizing wild-type JAB and CIS3 (SOCS3). The SOCS box interaction with Elongin BC stabilizes SOCS1 itself; overexpression of Elongin BC canceled F59D-JAB-induced destabilization of wild-type JAB. Transgenic mice with F59D-JAB, T cell stimulation assays, 293 cell cotransfection, protein stability assays, Elongin BC overexpression The Journal of biological chemistry Medium 11522790
2004 JAKs (Jak1 and Jak2) bind to TNF receptor-1 (TNFR-1) and are activated by TNF-α. SOCS1 suppresses TNF-α-induced apoptosis by inhibiting JAK activation and caspase activation downstream. In JAK-deficient cell lines, DNA fragmentation and caspase-8 activation by TNF-α are reduced, establishing that JAKs participate in TNF-α-induced apoptosis signaling. Co-immunoprecipitation (JAK-TNFR1), SOCS1 overexpression, JAK-deficient cell lines, caspase activity assays International immunology Medium 15173123
2013 SOCS1 promotes nuclear redistribution and K63-ubiquitylation of VHL in response to DNA double-strand breaks. Loss of VHL or VHL mutations that compromise its K63-ubiquitylation attenuates the DNA-damage response, resulting in decreased homologous recombination repair. Ubiquitylation assays (K63-specific), subcellular fractionation/localization, VHL mutant analysis, DNA repair assays Oncogene Medium 23455319
2013 SOCS1 mediates ubiquitylation and degradation of the GM-CSF receptor β-common (βc) signaling subunit (GMRβc), attenuating GM-CSF-induced downstream signaling. Ubiquitylation assays, protein degradation assays, signaling readouts (downstream GM-CSF pathway) PloS one Medium 24086733
2012 Bcr-Abl tyrosine phosphorylates SOCS1 mainly on Tyr155 and Tyr204, which is associated with SOCS1 binding to Bcr-Abl. This phosphorylation diminishes SOCS1 inhibitory effects on JAK and STAT5 activation. Disruption of SOCS1 tyrosine phosphorylation impaired Bcr-Abl-mediated tumorigenesis in vivo and blocked Bcr-Abl bone marrow transformation. Mass spectrometry, site-directed mutagenesis, co-immunoprecipitation, STAT5/JAK phosphorylation assays, nude mouse tumorigenesis assay, bone marrow transformation assay Neoplasia High 22787435
2019 SOCS1 Y80 in the SH2 domain is phosphorylated by SRC family kinases; phosphomimetic substitution at Y80 inhibits SOCS1-p53 interaction and abolishes p53 transcriptional activity stimulation, growth arrest, and cellular senescence. Mass spectrometry confirmed Y80 phosphorylation in cells. SRC family kinase inhibitors potentiated the SOCS1-p53 pathway. In lymphomas overexpressing SOCS1, constitutive SRC family kinase activation leads to SOCS1 Y80 phosphorylation and cytoplasmic SOCS1 localization. Mass spectrometry, site-directed mutagenesis (phosphomimetic Y80E), co-immunoprecipitation, p53 transcriptional activity assays, senescence assays, kinase library screen, IHC with phospho-specific antibody Cancer research High 31101761
2008 Glucocorticoid receptor (GR) and SOCS1 form an intracellular complex; the interaction requires the SH2 domain of SOCS1 and the ligand-binding domain of GR. GC stimulation increases nuclear levels of SOCS1. SOCS1 binding to GR negatively influences transcription of GR-regulated genes FKBP5 and MKP1, as shown by IFNγ-induced SOCS1 inhibiting their expression and enhanced expression in SOCS1-deficient fibroblasts. Co-immunoprecipitation, subcellular fractionation, SH2 domain deletion mutants, SOCS1-deficient MEFs, gene expression assays The Journal of biological chemistry Medium 18524780
2017 SOCS1 acts as a negative regulator of macrophage metabolic reprogramming during sepsis. Myeloid-specific SOCS1 deletion increases glycolysis (elevated lactic acid, hexokinase, LDHA, GLUT1 expression) in septic macrophages via the STAT3/HIF-1α/glycolysis axis. A SOCS1 KIR-blocking peptide (iKIR) increases CLP-induced mortality, confirming that SOCS1 KIR domain activity is required for this function. Myeloid-specific conditional SOCS1 knockout mice, cecal ligation and puncture model, metabolic measurements (lactate, glycolytic enzyme expression), KIR peptide inhibitor (iKIR), STAT3/HIF-1α pathway analysis, glycolysis inhibitor rescue JCI insight High 28679957
2010 Threonine phosphorylation of SOCS1 by Pim-1 (induced by Pasteurella multocida Toxin) disrupts SOCS1 E3 ubiquitin ligase activity toward JAK2, preventing JAK2 from being marked for proteasomal degradation. This leads to increased JAK2 and STAT3 activity and increased anchorage-independent growth. Pim-1 kinase coexpression, SOCS1 phosphorylation analysis, JAK2 ubiquitination/degradation assays, STAT3 activity assays, anchorage-independent growth assay Cellular microbiology Medium 20633028
2008 SOCS1 regulates IFN-dependent pathways (IFN-β production and STAT1 phosphorylation) downstream of TLR4 in human monocytes, but does not regulate early NF-κB activation or DNA binding capacity in LPS-stimulated human monocytes. Adenoviral SOCS1 overexpression in primary human monocytes, NF-κB DNA-binding assays, STAT1 phosphorylation assays, IFN-β mRNA/protein measurement, cytokine ELISA Journal of immunology Medium 19017994
2017 SOCS1 regulates cellular senescence and ferroptosis through p53 target genes. SOCS1 reduces expression of the cystine transporter SLC7A11 and glutathione levels, sensitizing cells to ferroptosis. This effect requires SOCS1 sufficiency and correlates with its ability to regulate p53 target gene expression. Transcriptome analysis, SOCS1 overexpression/inhibition, SLC7A11 expression assays, glutathione measurement, ferroptosis assays Aging Medium 29081404
2020 Heterozygous germline loss-of-function mutations in SOCS1 cause haploinsufficiency resulting in enhanced STAT1, STAT3 (to a lesser degree), and STAT5/STAT6 activation in patient-derived lymphocytes in response to IFN-γ, IL-2, and IL-4. This enhanced STAT activation was reverted by JAK1/JAK2 inhibitor ruxolitinib, establishing JAK-STAT hyperactivation as the cellular mechanism of disease. Whole-exome/genome sequencing, patient-derived lymphocyte stimulation assays, STAT phosphorylation assays, JAK inhibitor (ruxolitinib) rescue Nature communications High 33087723
2008 SOCS1 regulates CCR7 expression and T cell trafficking to peripheral tissues. In SOCS1-deficient mice, CCR7 is markedly reduced on T cells correlating with hyperactivation of STAT6. Forced SOCS1 overexpression in T cells upregulates CCR7 and enhances chemotaxis toward CCL19/CCL21. CCR6 and CXCR3 are also upregulated on SOCS1-deficient T cells. SOCS1 KO, STAT1 KO, STAT6 KO mice; stable SOCS1 overexpression/deletion in T cells; flow cytometry; chemotaxis assay Journal of immunology Medium 18606672

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. The Journal of biological chemistry 702 12228220
1999 The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. The EMBO journal 584 10064597
2002 SOCS-1 participates in negative regulation of LPS responses. Immunity 517 12433373
2002 SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 505 12433365
2018 The molecular basis of JAK/STAT inhibition by SOCS1. Nature communications 373 29674694
2001 The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2. The Journal of biological chemistry 264 11278610
2009 SOCS1 and SOCS3 in the control of CNS immunity. Trends in immunology 237 19643666
1998 Three distinct domains of SSI-1/SOCS-1/JAB protein are required for its suppression of interleukin 6 signaling. Proceedings of the National Academy of Sciences of the United States of America 195 9789053
2002 Pim serine/threonine kinases regulate the stability of Socs-1 protein. Proceedings of the National Academy of Sciences of the United States of America 167 11854514
1998 A Janus kinase inhibitor, JAB, is an interferon-gamma-inducible gene and confers resistance to interferons. Blood 160 9716595
2004 SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. The Journal of experimental medicine 159 15197228
1999 Cutting edge: SOCS-1 is a potent inhibitor of IL-4 signal transduction. Journal of immunology (Baltimore, Md. : 1950) 134 10201892
2020 Early-onset autoimmunity associated with SOCS1 haploinsufficiency. Nature communications 125 33087723
2009 SOCS1 links cytokine signaling to p53 and senescence. Molecular cell 122 20005840
2008 Expression and functional significance of SOCS-1 and SOCS-3 in astrocytes. Journal of immunology (Baltimore, Md. : 1950) 112 18713987
2001 JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling. Blood 110 11133764
2002 The tumor suppressor activity of SOCS-1. Oncogene 108 12080466
2004 Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3. Blood 106 14764533
2017 Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type. Molecular medicine reports 101 28901399
2007 IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro. American journal of physiology. Gastrointestinal and liver physiology 101 17204547
2002 TRIM8/GERP RING finger protein interacts with SOCS-1. The Journal of biological chemistry 98 12163497
2006 SOCS1: a potent and multifaceted regulator of cytokines and cell-mediated inflammation. Tissue antigens 96 16451196
1997 SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. The Journal of biological chemistry 95 9341160
2017 SOCS1 regulates senescence and ferroptosis by modulating the expression of p53 target genes. Aging 91 29081404
2007 Reciprocal regulation of SOCS 1 and SOCS3 enhances resistance to ionizing radiation in glioblastoma multiforme. Clinical cancer research : an official journal of the American Association for Cancer Research 86 17438093
2012 Role of SOCS1 in tumor progression and therapeutic application. International journal of cancer 73 22025331
2007 Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma. Gut 72 17376806
2004 Expression of SOCS-1, suppressor of cytokine signalling-1, in human melanoma. The Journal of investigative dermatology 69 15373779
2019 Therapeutic Implication of SOCS1 Modulation in the Treatment of Autoimmunity and Cancer. Frontiers in pharmacology 66 31105556
2016 SOCS1 in cancer: An oncogene and a tumor suppressor. Cytokine 63 26811119
2001 A mutant form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family proteins through the SOCS-box. The Journal of biological chemistry 59 11522790
2000 Regulation of SOCS-1 expression by translational repression. The Journal of biological chemistry 58 10764816
2003 Regulation of cytokine receptor signaling by SOCS1. Immunological reviews 54 12670405
2004 Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers. Japanese journal of clinical oncology 50 15121754
2008 SOCS1 regulates the IFN but not NFkappaB pathway in TLR-stimulated human monocytes and macrophages. Journal of immunology (Baltimore, Md. : 1950) 49 19017994
1999 SOCS-1, -2, -3: selective targets and functions downstream of the prolactin receptor. Molecular and cellular endocrinology 49 10630404
2002 Combined hypermethylation and chromosome loss associated with inactivation of SSI-1/SOCS-1/JAB gene in human hepatocellular carcinomas. Cancer letters 47 12183076
2000 SOCS-1 can suppress CD3zeta- and Syk-mediated NF-AT activation in a non-lymphoid cell line. FEBS letters 47 10788618
2019 Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3. PloS one 45 30811476
1998 The CIS/JAB family: novel negative regulators of JAK signaling pathways. Leukemia 45 9844915
2013 miR-19a promotes cell growth and tumorigenesis through targeting SOCS1 in gastric cancer. Asian Pacific journal of cancer prevention : APJCP 44 23621248
2004 SOCS-1 localizes to the microtubule organizing complex-associated 20S proteasome. Molecular and cellular biology 44 15456882
2004 SOCS-1 suppresses TNF-alpha-induced apoptosis through the regulation of Jak activation. International immunology 41 15173123
2013 K63-ubiquitylation of VHL by SOCS1 mediates DNA double-strand break repair. Oncogene 40 23455319
2010 Epigenetic alteration of the SOCS1 gene in hepatocellular carcinoma. Swiss medical weekly 40 20648401
2017 SOCS1 is a negative regulator of metabolic reprogramming during sepsis. JCI insight 38 28679957
2017 Resveratrol Attenuates Microglial Activation via SIRT1-SOCS1 Pathway. Evidence-based complementary and alternative medicine : eCAM 37 28781601
2011 Expression of SOCS1-7 and CIS mRNA in porcine tissues. Veterinary immunology and immunopathology 37 21872343
2020 lncRNA TUG1 regulates ulcerative colitis through miR-142-5p/SOCS1 axis. Microbial pathogenesis 36 32173492
2014 Resveratrol counteracts lipopolysaccharide-mediated microglial inflammation by modulating a SOCS-1 dependent signaling pathway. Toxicology in vitro : an international journal published in association with BIBRA 36 24882063
2009 SOCS1 protects protein tyrosine phosphatases by thioredoxin upregulation and attenuates Jaks to suppress ROS-mediated apoptosis. Oncogene 36 19561639
2019 Hepatocyte growth control by SOCS1 and SOCS3. Cytokine 34 31154249
2010 Enforced SOCS1 and SOCS3 expression attenuates Lck-mediated cellular transformation. International journal of oncology 34 20372794
2012 A requirement for SOCS-1 and SOCS-3 phosphorylation in Bcr-Abl-induced tumorigenesis. Neoplasia (New York, N.Y.) 33 22787435
2001 Induction of JAB/SOCS-1/SSI-1 and CIS3/SOCS-3/SSI-3 is involved in gp130 resistance in cardiovascular system in rat treated with cardiotrophin-1 in vivo. Circulation research 33 11304496
2000 The JAK-inhibitor, JAB/SOCS-1 selectively inhibits cytokine-induced, but not v-Src induced JAK-STAT activation. Oncogene 33 11032030
2019 SOCS1 and its Potential Clinical Role in Tumor. Pathology oncology research : POR 32 30761449
2018 A cell penetrating peptide from SOCS-1 prevents ocular damage in experimental autoimmune uveitis. Experimental eye research 32 30048621
2017 SOCS1: Regulator of T Cells in Autoimmunity and Cancer. Current topics in microbiology and immunology 32 28900678
2014 Respiratory syncytial virus NS1 protein degrades STAT2 by inducing SOCS1 expression. Intervirology 31 24480984
2001 The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells. Oncogene 31 11314018
2023 A mutual regulatory loop between miR-155 and SOCS1 influences renal inflammation and diabetic kidney disease. Molecular therapy. Nucleic acids 30 37842165
2021 Bortezomib Sustains T Cell Function by Inducing miR-155-Mediated Downregulation of SOCS1 and SHIP1. Frontiers in immunology 30 33717088
2019 Human microRNA-30 inhibits influenza virus infection by suppressing the expression of SOCS1, SOCS3, and NEDD4. Cellular microbiology 30 31876380
2006 SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes. Journal of autoimmunity 30 17045460
2015 Tumour-promoting role of SOCS1 in colorectal cancer cells. Scientific reports 29 26391193
2008 SOCS-1 inhibits TNF-alpha-induced cardiomyocyte apoptosis via ERK1/2 pathway activation. Inflammation 29 18330685
2006 Overproduction of collagen and diminished SOCS1 expression are causally linked in fibroblasts from idiopathic pulmonary fibrosis. Biochemical and biophysical research communications 29 17198680
2022 N6-methyladenosine of Socs1 modulates macrophage inflammatory response in different stiffness environments. International journal of biological sciences 28 36263168
2021 IFN-γ inhibits ovarian cancer progression via SOCS1/JAK/STAT signaling pathway. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 28 34275119
2021 One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency. Frontiers in immunology 26 34421895
2018 SOCS-1 Suppresses Inflammation Through Inhibition of NALP3 Inflammasome Formation in Smoke Inhalation-Induced Acute Lung Injury. Inflammation 26 29907905
2008 Interaction and functional interference of glucocorticoid receptor and SOCS1. The Journal of biological chemistry 26 18524780
2016 miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia. Blood cancer journal 25 26990535
2014 SOCS1 and regulation of regulatory T cells plasticity. Journal of immunology research 25 25133199
2000 The janus kinase inhibitor, Jab/SOCS-1, is an interferon-gamma inducible gene and determines the sensitivity to interferons. Leukemia & lymphoma 24 10811447
2024 SOCS1 and SOCS3 as key checkpoint molecules in the immune responses associated to skin inflammation and malignant transformation. Frontiers in immunology 23 38975347
2018 Association between methylation of tumor suppressor gene SOCS1 and acute myeloid leukemia. Oncology reports 23 29916533
2016 TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice. Journal of immunology (Baltimore, Md. : 1950) 23 27798161
2021 miR-122 promotes virus-induced lung disease by targeting SOCS1. JCI insight 22 33830082
2017 Egr2 enhances insulin resistance via JAK2/STAT3/SOCS-1 pathway in HepG2 cells treated with palmitate. General and comparative endocrinology 22 28842216
2013 Multiple roles of SOCS proteins: differential expression of SOCS1 and SOCS3 in atherosclerosis. International journal of molecular medicine 22 23545584
2011 Role of SOCS-1 Gene on Melanoma Cell Growth and Tumor Development. Translational oncology 22 21461173
2019 RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma. Cancer biomarkers : section A of Disease markers 20 30689554
2014 A MyD88-JAK1-STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus. Cellular & molecular immunology 20 25399770
2013 SOCS-1 mediates ubiquitylation and degradation of GM-CSF receptor. PloS one 20 24086733
2016 Promoter methylation and expression of SOCS-1 affect clinical outcome and epithelial-mesenchymal transition in colorectal cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 27133036
2008 SOCS1 regulates CCR7 expression and migration of CD4+ T cells into peripheral tissues. Journal of immunology (Baltimore, Md. : 1950) 19 18606672
2024 Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment. Journal of medicinal chemistry 17 39110625
2021 MicroRNA-30e-5p Regulates SOCS1 and SOCS3 During Bacterial Infection. Frontiers in cellular and infection microbiology 17 33585275
2020 Identification of a Human SOCS1 Polymorphism That Predicts Rheumatoid Arthritis Severity. Frontiers in immunology 17 32670294
2019 Phosphorylation of SOCS1 Inhibits the SOCS1-p53 Tumor Suppressor Axis. Cancer research 17 31101761
2019 The impact of SOCS1 mutations in diffuse large B-cell lymphoma. British journal of haematology 17 31407320
2010 Pasteurella multocida Toxin-induced Pim-1 expression disrupts suppressor of cytokine signalling (SOCS)-1 activity. Cellular microbiology 17 20633028
2008 SOCS-1 deficiency does not prevent diet-induced insulin resistance. Biochemical and biophysical research communications 17 18929539
2023 SOCS1 Deficiency Promotes Hepatocellular Carcinoma via SOCS3-Dependent CDKN1A Induction and NRF2 Activation. Cancers 16 36765862
2021 miR-155-5p predictive role to decelerate foam cell atherosclerosis through CD36, VAV3, and SOCS1 pathway. Non-coding RNA research 16 33869908
2017 Expression of SOCS1 and the downstream targets of its putative tumor suppressor functions in prostate cancer. BMC cancer 16 28235401
2015 miR-19a and SOCS-1 expression in the differential diagnosis of laryngeal (glottic) verrucous squamous cell carcinoma. Journal of clinical pathology 16 26502748
2005 SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo. Circulation journal : official journal of the Japanese Circulation Society 15 16247220

Missed literature

Know a paper Affinage missed for SOCS1? Flag it for the maintainers and the community.

No submissions yet.