Affinage

TSC22D3

TSC22 domain family protein 3 · UniProt Q99576

Length
134 aa
Mass
14.8 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TSC22D3 (GILZ) is a glucocorticoid-inducible leucine-zipper protein that executes the anti-inflammatory and immunosuppressive program of glucocorticoids by physically intercepting multiple pro-inflammatory and proliferative signaling nodes (PMID:11397794, PMID:17169985, PMID:17492054). It transcriptionally couples to upstream hormonal control: glucocorticoid receptor binding to GREs drives GILZ induction (including ligand-independent GR activation), and additional inputs—FoxO3 upon IL-2 withdrawal, SREBP1/HIF1α, and USF1/2 at an E-box—tune its expression, while estradiol/ERα and type I IFN (JAK1/Tyk2-dependent) displace GR to repress it (PMID:15031210, PMID:31055798, PMID:22792400, PMID:23183181, PMID:36505447). Mechanistically, GILZ acts largely by sequestration and direct binding: homodimerization via its leucine zipper plus the C-terminal PER domain is required for binding NF-κB p65 and inhibiting NF-κB-driven transcription, its N-terminal 60 residues bind c-Fos/c-Jun to block AP-1, and its TSC box engages Ras and Raf to form a trimeric complex that dampens ERK/AKT signaling and proliferation (PMID:17169985, PMID:11397794, PMID:17492054). It further binds STAT1 to block its nuclear translocation and suppress type I IFN/ISG responses, promotes Crm1-dependent nuclear exclusion of FOXO3, binds Smad2 to promote TGF-β/FoxP3-driven regulatory T cell generation, and represses adipogenic lineage genes (PPARγ2) through C/EBP sites while favoring osteogenic commitment (PMID:35810690, PMID:20018851, PMID:24703841, PMID:12671681, PMID:24860090). The long isoform L-GILZ binds MDM2 to stabilize p53, and in spermatogonia GILZ forms TSC22D-family complexes that restrain ERK and mTORC1 to maintain stem-cell homeostasis—Gilz loss causes germ-cell exhaustion and male sterility (PMID:25168242, PMID:30126904, PMID:22110132). Genetic loss-of-function across tissues establishes GILZ as a brake on immune and proliferative output, including B-cell survival via NF-κB/Bcl-2 and neutrophil oxidative activation, and as a stress/glucocorticoid-driven suppressor of antitumor immunity in dendritic cells (PMID:26276664, PMID:30371949, PMID:31501614). GILZ stability is itself controlled post-translationally through caspase-8-linked SUMO-1 conjugation and K48-ubiquitylation (PMID:20671745, PMID:29146236).

Mechanistic history

Synthesis pass · year-by-year structured walk · 36 steps
  1. 2001 High

    Established the first direct molecular mechanism for GILZ as a transcriptional brake, showing it binds AP-1 components and requires leucine-zipper-mediated dimerization, defining its mode of action on immune gene promoters.

    Evidence Recombinant in vitro interaction assays, domain-deletion mutants, and reporter assays in Jurkat/primary T cells

    PMID:11397794

    Open questions at the time
    • Did not address NF-κB or other transcription factor targets
    • No in vivo validation of AP-1 inhibition
  2. 2002 Medium

    Extended GILZ's inhibitory repertoire to NF-κB, linking glucocorticoid/IL-10 signaling to suppression of macrophage costimulatory and chemokine genes.

    Evidence Co-immunoprecipitation and GILZ transfection in THP-1 macrophage-like cells with flow cytometry/RT-PCR readouts

    PMID:12393603

    Open questions at the time
    • Domain requirements for p65 binding not defined here
    • Single cell line
  3. 2003 High

    Demonstrated GILZ acts as a sequence-specific transcriptional repressor at C/EBP sites, mechanistically explaining glucocorticoid inhibition of adipocyte differentiation.

    Evidence Promoter binding assays and ectopic expression in mesenchymal cells with adipogenic differentiation readouts

    PMID:12671681

    Open questions at the time
    • No structural basis for promoter recognition
    • Direct DNA-binding versus C/EBP tethering not fully resolved
  4. 2004 High

    Placed GILZ in a FoxO3-driven survival circuit, showing reciprocal regulation (FoxO3 induces GILZ; GILZ inhibits FoxO3) controlling Bim and T-cell apoptosis.

    Evidence GILZ promoter FHRE mutagenesis with gain/loss-of-function in CTLL-2 cells and apoptosis assays

    PMID:15031210

    Open questions at the time
    • Mechanism of FoxO3 inhibition not defined at this stage
  5. 2004 Medium

    Established GILZ as a pro-apoptotic regulator of thymocyte selection in vivo through Bcl-xL downregulation and caspase activation.

    Evidence T-cell GILZ transgenic mice and TAT-GILZ protein delivery with caspase/Bcl-xL readouts

    PMID:15319285

    Open questions at the time
    • Molecular target driving Bcl-xL loss not identified
    • Single lab
  6. 2006 High

    Defined the bipartite structural requirement (leucine zipper plus PER domain) for GILZ/p65 binding, mechanistically dissecting NF-κB inhibition.

    Evidence In vitro and in vivo co-IP with multiple GILZ deletion/point mutants and NF-κB reporters

    PMID:17169985

    Open questions at the time
    • No co-crystal structure of GILZ/p65
    • Stoichiometry of the inhibitory complex unresolved
  7. 2006 High

    Identified the TSC box as the Ras-binding module and showed GILZ forms a Ras/Raf trimeric complex, connecting GILZ to glucocorticoid antiproliferative effects.

    Evidence In vitro binding, co-IP and colocalization in primary T cells, domain mutants, siRNA, and transformation assays

    PMID:17492054

    Open questions at the time
    • Whether GILZ blocks Ras GTPase activity or only effector coupling not resolved
  8. 2007 Medium

    Showed GILZ governs mesenchymal lineage choice, promoting osteogenesis at the expense of adipogenesis via lineage marker reprogramming.

    Evidence GILZ overexpression and knockdown in mouse MSCs with differentiation assays and lineage marker RT-PCR

    PMID:18084007

    Open questions at the time
    • Direct transcriptional targets in osteogenic program not mapped here
    • Single lab
  9. 2007 Medium

    Extended GILZ transcriptional inhibition to the myogenic program through MyoD/HDAC1 regulation, explaining glucocorticoid anti-myogenic effects.

    Evidence C2C12 differentiation with GILZ/L-GILZ gain/loss-of-function and co-IP with MyoD/HDAC1

    PMID:20124407

    Open questions at the time
    • Direct versus indirect binding to MyoD not fully separated
    • Single lab
  10. 2008 Medium

    Refined GILZ's NF-κB inhibition mechanism in MSCs, showing it blocks p65 nuclear translocation to suppress COX-2.

    Evidence Retroviral overexpression/shRNA, NF-κB translocation imaging/fractionation, COX-2 reporters

    PMID:17910039

    Open questions at the time
    • Apparent discrepancy with later reports that GILZ does not affect p65 translocation
  11. 2009 Medium

    Resolved how GILZ inhibits FOXO3 without binding it, identifying Crm1-dependent nuclear exclusion as the mechanism.

    Evidence Live-cell imaging, leptomycin B treatment, FOXO reporters and fractionation in HL-60/CTLL-2

    PMID:20018851

    Open questions at the time
    • Intermediate kinase/adaptor linking cytoplasmic GILZ to FOXO3 export unknown
  12. 2010 Medium

    Defined post-translational control of GILZ stability, linking glucocorticoid-induced caspase-8 to SUMO-1 conjugation via Ubc9 and protection from proteasomal degradation.

    Evidence In vitro GILZ–Ubc9/SUMO-1 binding, co-IP, caspase-8-deficient thymocytes, proteasome inhibition

    PMID:20671745

    Open questions at the time
    • Functional consequence of GILZ SUMOylation on activity not established
    • SUMO acceptor lysine not mapped
  13. 2011 Medium

    Distinguished GILZ inhibition of mTORC2 (not mTORC1), connecting it to AKT-S473/FoxO3a/Bim-driven apoptosis and drug sensitization in BCR-ABL+ cells.

    Evidence Reciprocal co-IP with mTOR complex components, AKT phosphorylation, FoxO3a reporters in CML cells

    PMID:21804606

    Open questions at the time
    • Binding interface with mTORC2 not mapped
    • Apparent contrast with later spermatogonial mTORC1 control
  14. 2011 High

    Established GILZ as essential for spermatogenesis in vivo, with KO germline loss linked to Ras pathway (ERK/Akt) hyperactivation.

    Evidence Gilz knockout mice with IHC, ERK/Akt phosphorylation, and spermatogenesis phenotyping

    PMID:22110132

    Open questions at the time
    • Whether germline defect is cell-intrinsic versus somatic not resolved here
  15. 2012 High

    Confirmed and elaborated the Gilz-null testis phenotype while showing minimal baseline immune deficit, distinguishing tissue-specific essentiality.

    Evidence Conditional Tsc22d3-2 KO with testis histology, TUNEL, hormone and renal electrolyte measurements

    PMID:22556341

    Open questions at the time
    • Renal sodium/water handling mechanism not defined
    • Immune phenotypes emerge mainly under challenge
  16. 2012 Medium

    Showed ligand-independent GR can transactivate GILZ at GREs, broadening the upstream control of GILZ to non-glucocorticoid (alcohol) contexts.

    Evidence EMSA for GR–GRE, GRE reporter mutagenesis, CRISPR GR KO, GILZ siRNA

    PMID:28638383

    Open questions at the time
    • How unliganded GR is activated by alcohol not mechanistically resolved
  17. 2012 Medium

    Identified a Rho-GTPase/MAPK/USF input controlling GILZ, showing bacterial toxins induce GILZ through an E-box bound by USF1/2.

    Evidence GILZ promoter reporters, EMSA for USF binding, USF siRNA, MAPK inhibitors, Rho manipulation

    PMID:22792400

    Open questions at the time
    • Functional consequence of toxin-induced GILZ for host defense not defined here
  18. 2012 High

    Identified estradiol/ERα as a repressor of GILZ that reduces GR occupancy at the promoter, defining cross-talk between estrogen and glucocorticoid control.

    Evidence ChIP for GR/ERα at GILZ promoter, ERα siRNA, ER antagonist, in vivo uterus model

    PMID:23183181

    Open questions at the time
    • Mechanism by which ERα displaces GR not structurally defined
  19. 2013 Medium

    Clarified that GILZ can inhibit NF-κB at the level of p65 DNA binding (not translocation) and broadly dampens MAPK signaling to limit endothelial leukocyte recruitment.

    Evidence GILZ transfection in HUVECs, NF-κB DNA-binding versus translocation assays, MAPK and MKP-1 readouts, adhesion assays

    PMID:23729444

    Open questions at the time
    • Reconciliation with translocation-blocking reports unresolved
    • Transfection system only
  20. 2013 Medium

    Placed GILZ induction under corepressor control, showing DC-SCRIPT restrains GR-driven GILZ expression in dendritic cells.

    Evidence Co-IP of DC-SCRIPT with GR and DC-SCRIPT knockdown in monocyte-derived DCs

    PMID:23440419

    Open questions at the time
    • Direct versus indirect effect on GILZ locus not separated
  21. 2013 Medium

    Showed GILZ mediates glucocorticoid suppression of airway epithelial repair via Raf-1/MEK/ERK inhibition, linking GILZ to tissue regeneration outcomes.

    Evidence GILZ siRNA, pRaf/pMEK/pERK Western blot, wound-healing and proliferation assays

    PMID:23573276

    Open questions at the time
    • Whether GILZ acts via direct Raf binding here not tested
  22. 2014 High

    Defined a p53-stabilizing function for L-GILZ via MDM2 binding, connecting GILZ to tumor suppression.

    Evidence Co-IP with p53/MDM2, ubiquitination assays, isogenic p53+/+ vs p53-/- cells, xenografts, L-GILZ siRNA

    PMID:25168242

    Open questions at the time
    • Isoform specificity (L-GILZ vs GILZ) for MDM2 binding interface not mapped
  23. 2014 High

    Identified GILZ as a positive regulator of TGF-β/Smad2 signaling driving FoxP3+ regulatory T-cell generation, defining a pro-tolerogenic axis.

    Evidence GILZ transgenic and KO mice, co-IP with Smad2, Smad2 phosphorylation, FoxP3 reporter, intestinal inflammation model

    PMID:24703841

    Open questions at the time
    • How GILZ promotes Smad2 phosphorylation mechanistically not defined
  24. 2014 Medium

    Confirmed in vivo that GILZ drives osteogenic over adipogenic commitment through C/EBP-mediated PPARγ repression, with transgenic mice showing increased bone mass.

    Evidence Co-IP with C/EBPs, PPARγ reporters, collagen-promoter GILZ transgenic mice, bone histomorphometry

    PMID:24860090

    Open questions at the time
    • Direct DNA contact versus C/EBP tethering at PPARγ not separated
  25. 2015 High

    Established a B-cell-intrinsic role for GILZ in restraining survival, with KO lymphocytosis tied to elevated NF-κB activity and Bcl-2.

    Evidence Global and B-cell-specific gilz KO, flow cytometry, apoptosis assays, NF-κB reporter, Bcl-2 Western blot

    PMID:26276664

    Open questions at the time
    • Direct molecular link from GILZ loss to Bcl-2 induction not fully resolved
  26. 2016 Medium

    Identified post-transcriptional control of GILZ by HuR, explaining curcumin-driven anti-inflammatory GILZ induction independent of transcription.

    Evidence RNA immunoprecipitation of HuR–GILZ mRNA, HuR overexpression, GILZ KO macrophages, inflammatory readouts

    PMID:27629417

    Open questions at the time
    • HuR binding element on GILZ mRNA not mapped
  27. 2017 Medium

    Revealed a nuclear, transcription-activating mode for GILZ in primed MSCs, binding iNOS and Activin βA promoters to repress Th17 differentiation.

    Evidence ChIP at iNOS/Activin βA promoters, nuclear translocation imaging, Activin A ELISA, Smad2/3 readouts, adoptive transfer

    PMID:29344311

    Open questions at the time
    • Signals controlling cytoplasmic-to-nuclear GILZ shift not defined
    • Direct versus cofactor-dependent DNA binding unclear
  28. 2017 Medium

    Showed viral immune evasion converges on GILZ stability, with IBDV VP4 suppressing GILZ K48-ubiquitylation to limit IFN-β.

    Evidence K48-linkage-specific ubiquitylation assays, VP4 R41G mutant, IBDV infection, IFN-β reporters

    PMID:29146236

    Open questions at the time
    • E3 ligase and deubiquitylase acting on GILZ not identified
  29. 2018 High

    Defined the spermatogonial stem-cell mechanism, showing GILZ forms TSC22D-family complexes and restrains ERK/mTORC1, with mTOR inhibition rescuing germline failure.

    Evidence Adult conditional Gilz KO, mTOR inhibitor rescue, USP9X analysis, co-IP with TSC22D proteins, ERK phosphorylation

    PMID:30126904

    Open questions at the time
    • Direct GILZ–mTORC1 regulatory link versus ERK-mediated effect not separated
    • Role of USP9X mechanistically incomplete
  30. 2018 Medium

    Established GILZ as a brake on neutrophil effector function through MAPK and NOX2/p47phox suppression.

    Evidence GILZ-KO neutrophils, Candida and DNBS colitis models, MAPK and oxidative burst/phagocytosis assays

    PMID:30371949

    Open questions at the time
    • Direct GILZ target controlling NOX2 not identified
  31. 2019 High

    Connected psychological stress to immunosuppression via DC-intrinsic GILZ, showing corticosterone-induced GILZ blocks type I IFN and abolishes antitumor therapy control.

    Evidence Social-defeat stress model, DC-specific Tsc22d3 transgenic and conditional KO mice, GR antagonist, tumor challenge

    PMID:31501614

    Open questions at the time
    • Molecular target of GILZ in the DC IFN block not defined in this study
  32. 2019 Medium

    Identified a metabolic/hypoxic transcriptional circuit, with SREBP1 and HIF1α inducing GILZ, which in turn binds and activates the FVII locus.

    Evidence ChIP for HIF1α at TSC22D3 and GILZ at FVII in xenografts, GILZ siRNA, SREBP1 manipulation, reporters

    PMID:31055798

    Open questions at the time
    • GILZ DNA-binding mode at FVII versus cofactor dependence unclear
  33. 2020 Medium

    Showed GILZ promotes ubiquitin-proteasomal degradation of HIF-1α, defining a glucocorticoid mechanism for HIF-1α turnover in disease tissue.

    Evidence Co-IP with HIF-1α, ubiquitination assays, TSC22D3 siRNA, in vivo diabetic retina model

    PMID:32150332

    Open questions at the time
    • Whether GILZ recruits a specific E3 ligase to HIF-1α not established
    • Apparent contrast with HIF1α-induced GILZ expression
  34. 2022 High

    Defined the molecular basis of GILZ suppression of type I IFN, showing direct STAT1 binding that blocks STAT1 nuclear translocation and ISG induction.

    Evidence Co-IP with STAT1, nuclear translocation assays, GILZ overexpression/KO in human PBMC, ISG reporters

    PMID:35810690

    Open questions at the time
    • STAT1-binding domain on GILZ not mapped
    • Effect on STAT2/STAT3 not addressed
  35. 2022 Medium

    Established a feedback antagonism whereby type I IFN suppresses GILZ via JAK1/Tyk2 by reducing GR occupancy at the GILZ locus.

    Evidence ChIP for GR at GILZ locus, JAK inhibitors, IFN treatment of human PBMCs, SLE patient correlation

    PMID:36505447

    Open questions at the time
    • Mechanism by which JAK signaling displaces GR not defined
  36. 2023 Medium

    Identified an ISGylation-dependent RNA-binding control of TSC22D3 mRNA, where RBM47 ISGylation at K329 negatively regulates GILZ expression.

    Evidence K329R knockin mice, nanobody-targeted site-specific RBM47 ISGylation in human cells, mRNA quantification, injury/tumor models

    PMID:38036512

    Open questions at the time
    • Whether RBM47 binds TSC22D3 mRNA directly not established
    • Mechanism of ISGylation-driven repression unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying structural and mechanistic account of how a single small leucine-zipper protein selects among its many binding partners (NF-κB, AP-1, Ras/Raf, STAT1, Smad2, MDM2, mTORC2, C/EBPs, HIF-1α) in a context-dependent manner remains unresolved.
  • No co-structure of GILZ with any partner
  • Determinants of partner selectivity across cell types unknown
  • Cytoplasmic-sequestration versus nuclear-DNA-binding switch not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 5 GO:0003677 DNA binding 3 GO:0140313 molecular sequestering activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 4 R-HSA-5357801 Programmed Cell Death 3
Partners
FOSHIF1AJUNMDM2RAF1RELASMAD2STAT1
Complex memberships
GILZ-TSC22D complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 GILZ directly interacts with c-Fos and c-Jun in vitro through its N-terminal 60-amino acid region, inhibiting AP-1 DNA binding; homodimerization of GILZ requires the leucine zipper domain. GILZ expression in Jurkat T cells blocks AP-1-driven, IL-2 promoter-driven, and FasL promoter-driven reporter constructs, and inhibits Egr-2/Egr-3-mediated FasL induction. Recombinant protein in vitro interaction assays, transient transfection reporter assays, domain-deletion mutants, anti-CD3-stimulated normal T cells The Journal of biological chemistry High 11397794
2002 In THP-1 macrophage-like cells treated with glucocorticoids or IL-10, GILZ associates with the p65 subunit of NF-κB, and GILZ transfection inhibits NF-κB function and suppresses expression of CD80, CD86, CCL5, CCL3, and TLR2. Co-immunoprecipitation in THP-1 cells, transfection of GILZ gene, flow cytometry, RT-PCR Blood Medium 12393603
2004 FoxO3 binding to Forkhead-responsive elements in the GILZ promoter is necessary for induction of GILZ expression upon IL-2 withdrawal. GILZ overexpression protects T cells from IL-2 withdrawal-induced apoptosis and inhibits Bim expression, while GILZ silencing accelerates cell death and enhances Bim. GILZ also inhibits FoxO3 transcriptional activity, creating a negative feedback loop. GILZ promoter characterization, FHRE mutagenesis, GILZ overexpression and siRNA knockdown in CTLL-2 cells, apoptosis assays, Western blot for Bim Blood High 15031210
2003 GILZ binds directly to tandem CCAAT/enhancer-binding protein (C/EBP) binding sites in the PPARγ2 promoter and acts as a sequence-specific transcriptional repressor, inhibiting PPARγ2 transcription and blocking glucocorticoid-induced adipocyte differentiation. Promoter binding assays, ectopic GILZ expression in mesenchymal cells, adipogenic differentiation assays, marker gene expression analysis EMBO reports High 12671681
2006 GILZ interacts directly with Ras in vitro and in vivo (co-immunoprecipitation and colocalization in primary T cells); interaction is mediated through the TSC box domain. GILZ forms a trimeric complex with Ras and Raf. These interactions reduce ERK1/2, AKT/PKB phosphorylation, Rb phosphorylation, and cyclin D1 expression, inhibiting Ras/Raf-dependent proliferation and NIH-3T3 transformation. GILZ silencing abrogates dexamethasone antiproliferative effects. In vitro binding assays, co-immunoprecipitation, colocalization imaging, GILZ domain mutants, siRNA knockdown, cell proliferation/transformation assays The Journal of clinical investigation High 17492054
2006 GILZ homo-dimerization via the leucine zipper domain and the C-terminal PER domain (particularly residues 121–123) are both required for GILZ/p65 NF-κB interaction and inhibition of NF-κB transcriptional activity and IL-2 synthesis, as shown by in vitro and in vivo co-immunoprecipitation with multiple GILZ mutants. In vitro and in vivo co-immunoprecipitation, GILZ domain deletion/point mutants, NF-κB transcriptional reporter assays Nucleic acids research High 17169985
2007 GILZ and its isoform L-GILZ are expressed in skeletal muscle and C2C12 myoblasts; GILZ/L-GILZ overexpression inhibits myotube formation and reduces MyoD function and myogenin expression by binding and regulating MyoD/HDAC1 transcriptional activity. GILZ/L-GILZ silencing dampens glucocorticoid anti-myogenic effects. C2C12 myoblast differentiation assays, GILZ/L-GILZ overexpression and siRNA knockdown, co-immunoprecipitation of GILZ with MyoD/HDAC1, gene expression analysis The Journal of biological chemistry Medium 20124407
2007 GILZ overexpression in mouse mesenchymal stem cells increases alkaline phosphatase activity, mineralized nodule formation, and expression of Runx2/Cbfa1, alkaline phosphatase, type I collagen, and osteocalcin, while reducing PPARγ2 and C/EBPα. Gilz knockdown reduces MSC osteogenic differentiation capacity, indicating GILZ shifts MSC commitment from adipogenic to osteogenic. GILZ overexpression and siRNA knockdown in mouse MSCs, alkaline phosphatase activity assay, mineralized nodule formation, RT-PCR for lineage markers The Journal of biological chemistry Medium 18084007
2008 GILZ inhibits inflammatory cytokine (TNF-α and IL-1β)-induced COX-2 mRNA and protein expression in bone marrow mesenchymal stem cells by blocking NF-κB nuclear translocation and NF-κB-mediated COX-2 promoter activity. Knockdown of GILZ by shRNA reduces glucocorticoid inhibition of cytokine-induced COX-2. Retroviral GILZ overexpression, shRNA knockdown, COX-2 reporter assay, NF-κB nuclear translocation (fractionation/immunofluorescence), RT-PCR, Western blot Journal of cellular biochemistry Medium 17910039
2009 GILZ promotes nuclear exclusion of FOXO3 in a Crm1-dependent manner: GILZ expression (exclusively cytoplasmic) causes FOXO3 to relocalize from nucleus to cytoplasm, suppressing FOXO1/3/4 transcriptional activity and downregulating FOXO targets p27KIP1 and Bim. GILZ does not physically interact with FOXO3 and does not hinder FOXO3 DNA-binding directly. Fluorescence microscopy, Crm1 inhibitor (leptomycin B) treatment, FOXO-responsive reporter assays in HL-60 and CTLL-2 cells, subcellular fractionation The Journal of biological chemistry Medium 20018851
2010 Glucocorticoid-induced caspase-8 activation protects GILZ from proteasomal degradation and induces GILZ binding to SUMO-1; GILZ contains a SUMO-binding site, binds the SUMO E2-conjugating enzyme Ubc9 in vitro and in vivo, and co-immunoprecipitates with SUMO-1 in a caspase-8-dependent manner in thymocytes. In vitro binding assays (GILZ–Ubc9, GILZ–SUMO-1), co-immunoprecipitation, caspase-8 inhibition, proteasome inhibition, caspase-8-deficient thymocytes Cell death and differentiation Medium 20671745
2011 GILZ binds to and inhibits mTORC2 (but not mTORC1) in mouse and human BCR-ABL+ cells, suppressing Ser473-AKT phosphorylation and activating FoxO3a-mediated Bim transcription, thereby inducing apoptosis and reducing imatinib/dasatinib resistance. Co-immunoprecipitation of GILZ with mTORC2 components, AKT phosphorylation (Western blot), FoxO3a reporter assays, apoptosis assays, CD34+ CML stem cells Oncogene Medium 21804606
2011 L-GILZ (long isoform of GILZ) is highly expressed in spermatogonia and primary spermatocytes; Gilz knockout mice develop complete loss of germ cells and male sterility. GILZ deficiency leads to increased ERK and Akt phosphorylation (Ras pathway hyperactivation) and aberrant spermatogonial differentiation. Gilz knockout mice, immunohistochemistry, Western blot for ERK/Akt phosphorylation, apoptosis assays, spermatogenesis phenotyping The Journal of biological chemistry High 22110132
2012 Estradiol (E2) antagonizes glucocorticoid-induced GILZ gene expression through the estrogen receptor (ERα and ERβ): both GR and ERα are recruited to GRE-containing regions of the GILZ promoter, and E2 treatment decreases GR binding there. ER antagonist ICI 182,780 and ERα siRNA block E2-mediated GILZ repression. Chromatin immunoprecipitation (ChIP) for GR and ERα at GILZ promoter, siRNA knockdown of ERα, ER antagonist treatment, nascent RNA assay, in vivo mouse uterus model Endocrinology High 23183181
2013 GILZ overexpression in HUVECs inhibits TNF-induced NF-κB p65 DNA binding (without affecting p65 nuclear translocation), and suppresses p38, ERK, and JNK MAPK activation while increasing MKP-1. This reduces leukocyte rolling, adhesion, and transmigration, and decreases E-selectin, ICAM-1, CCL2, CXCL8, and IL-6. Transient transfection of GILZ in HUVECs, NF-κB reporter/DNA binding assays, p65 nuclear translocation imaging, MAPK phosphorylation (Western blot), leukocyte adhesion assays, MKP-1 quantification Journal of immunology Medium 23729444
2013 DC-SCRIPT coexists with GR in protein complexes and functions as a corepressor of GR-mediated transcription; DC-SCRIPT knockdown enhances GR-dependent upregulation of GILZ mRNA in dendritic cells. Co-immunoprecipitation of DC-SCRIPT with GR, DC-SCRIPT knockdown (siRNA), GILZ mRNA quantification in monocyte-derived DCs Journal of immunology Medium 23440419
2013 GILZ inhibits dexamethasone-suppressed airway epithelial repair by suppressing Raf-1, MEK1/2, and ERK1/2 phosphorylation (MAPK-ERK pathway), thereby inhibiting proliferation and migration. Silencing GILZ with siRNA reverses DEX-mediated inhibition of these pathway components and restores cell repair. siRNA knockdown, Western blot for pRaf/pMEK/pERK, wound-healing/migration assays, MTT proliferation assay, CFSE labeling PloS one Medium 23573276
2014 L-GILZ (long isoform) binds preferentially to MDM2 (in the presence of both p53 and MDM2) and interferes with p53/MDM2 complex formation, stabilizing p53 by decreasing its ubiquitination and increasing MDM2 ubiquitination, leading to p21 and PUMA induction and tumor growth suppression. Co-immunoprecipitation of L-GILZ with p53 and MDM2, ubiquitination assays, p53-proficient vs -deficient cell lines, xenograft tumor growth, siRNA knockdown of L-GILZ Cell death and differentiation High 25168242
2014 GILZ promotes TGF-β signaling by binding to Smad2 and promoting its phosphorylation, thereby activating FoxP3 expression and enabling GCs to cooperate with TGF-β in peripheral regulatory T cell (pTreg) generation. GILZ-deficient mice show impaired pTreg generation and increased intestinal inflammation. GILZ overexpression transgenic mice, Gilz knockout mice, co-immunoprecipitation of GILZ with Smad2, Smad2 phosphorylation assay, FoxP3 reporter, intestinal inflammation model Cell reports High 24703841
2014 GILZ physically interacts with C/EBPs and disrupts C/EBP-mediated PPARγ gene transcription, enhancing osteogenic while suppressing adipogenic differentiation. Transgenic mice expressing GILZ under a collagen promoter show increased bone mass, bone formation rate, and osteoblast numbers. Co-immunoprecipitation of GILZ with C/EBPs, PPARγ promoter reporter assays, transgenic mice, bone histomorphometry, MSC differentiation assays The Journal of biological chemistry Medium 24860090
2016 Curcumin induces GILZ protein expression post-transcriptionally via HuR: HuR binds GILZ mRNA (confirmed by RNA immunoprecipitation), and HuR overexpression increases GILZ protein but not mRNA. GILZ induction by curcumin mediates its anti-inflammatory effects (NF-κB/ERK inhibition, TNF-α reduction) in macrophages, as shown in GILZ KO macrophages. RNA immunoprecipitation (RIP) of HuR–GILZ mRNA, HuR overexpression, GILZ KO bone marrow-derived macrophages, NF-κB/ERK activity assays, TNF-α ELISA The Journal of biological chemistry Medium 27629417
2017 In immunoregulatory MSC (primed with IFN-γ and TNF-α), GILZ translocates to the nucleus and binds the promoters of iNOS and Activin βA to induce their expression. Activin A produced downstream of GILZ directly represses Th17 cell differentiation via Smad3/2 activation. ChIP of GILZ at iNOS and Activin βA promoters, nuclear translocation imaging, Activin A ELISA, Smad2/3 phosphorylation, adoptive transfer experiments Theranostics Medium 29344311
2018 GILZ deletion in adults causes exhaustion of GFRα1+ spermatogonial stem cells and germline degeneration associated with mTORC1 activation and reduced USP9X (a deubiquitylase required for spermatogenesis). mTOR inhibitor treatment rescues GFRα1+ spermatogonial failure. GILZ interacts with TSC22D family proteins (forming GILZ-TSC22D complexes) and controls ERK MAPK upstream of mTORC1. Adult conditional Gilz knockout, mTOR inhibitor rescue, USP9X expression analysis, co-immunoprecipitation of GILZ with TSC22D proteins, ERK phosphorylation analysis in cultured spermatogonia Development High 30126904
2018 GILZ restrains neutrophil activation by reducing ERK and p38 MAPK phosphorylation as well as NOX2 and p47phox activation; GILZ-KO neutrophils show enhanced phagocytosis, oxidative burst, and bacterial killing. GILZ-KO neutrophils, Candida albicans infection model, DNBS colitis model, MAPK phosphorylation (Western blot), oxidative burst assay, phagocytosis assay Journal of leukocyte biology Medium 30371949
2019 Stress-induced elevation of corticosterone upregulates Tsc22d3 (GILZ) in dendritic cells, which blocks type I IFN responses in DCs and IFN-γ+ T cell activation. Enforced DC-specific Tsc22d3 expression is sufficient to abolish therapeutic tumor control, and DC-specific Tsc22d3 deletion reverses the negative impact of stress/glucocorticoid on therapy outcomes. Social defeat stress mouse model, DC-specific Tsc22d3 transgenic and conditional KO mice, glucocorticoid receptor antagonist treatment, IFN response assays, tumor challenge models Nature medicine High 31501614
2019 Cholesterol deficiency under hypoxia activates SREBP1, which induces GILZ expression; GILZ in turn binds the FVII gene locus (confirmed by chromatin immunoprecipitation in xenograft tumors) and activates FVII transcription. GILZ expression is also induced by HIF1α. Reciprocal regulation between SREBP1 and GILZ was observed. ChIP in xenograft tumor samples (HIF1α at TSC22D3 locus; GILZ at FVII locus), GILZ siRNA knockdown, SREBP1 manipulation, luciferase reporter assays Thrombosis and haemostasis Medium 31055798
2020 Glucocorticoid-transactivated TSC22D3 (GILZ) interacts with HIF-1α (shown by co-immunoprecipitation) and promotes degradation of hypoxia-stabilized HIF-1α via the ubiquitin-proteasome pathway. TSC22D3 silencing reverses glucocorticoid-mediated HIF-1α ubiquitination and galectin-1 downregulation. Co-immunoprecipitation of TSC22D3 with HIF-1α, ubiquitination assay, TSC22D3 siRNA knockdown, HIF-1α protein stability assay, in vivo diabetic mouse retina model Journal of cellular and molecular medicine Medium 32150332
2022 GILZ directly binds STAT1 and prevents its nuclear translocation, thereby suppressing IFN-stimulated gene (ISG) expression and the type I IFN auto-amplification loop. GILZ deficiency permits a type I IFN signature, and GILZ overexpression prevents ISG upregulation in response to IFNα. Co-immunoprecipitation of GILZ with STAT1, nuclear translocation assay, GILZ overexpression and knockout in human PBMC, ISG reporter assays, TLR7/9 stimulation Journal of autoimmunity High 35810690
2022 Type I IFN suppresses GILZ expression and glucocorticoid induction of GILZ in a JAK1/Tyk2-dependent manner; IFN activation of this pathway reduces GR binding at key regulatory regions of the GILZ locus, as shown by ChIP. ChIP for GR at GILZ locus, JAK inhibitor treatment (tofacitinib/tosylate salt), in vitro IFN treatment of human PBMCs, large SLE patient dataset correlation Frontiers in immunology Medium 36505447
2004 GILZ overexpression in T-cell lineage transgenic mice decreases CD4+CD8+ thymocyte number, increases thymocyte apoptosis via reduced Bcl-xL expression and activated caspase-8 and caspase-3. TAT-GILZ fusion protein delivered into wild-type thymocytes decreases Bcl-xL and promotes apoptosis. Transgenic mice overexpressing GILZ in T cells, ex vivo thymocyte apoptosis assays, caspase activity assays, Bcl-xL Western blot, TAT-GILZ protein delivery Blood Medium 15319285
2012 Gilz knockout male mice develop severe testis dysplasia from postnatal day 10, increased apoptosis in seminiferous tubules, increased Leydig cells, and elevated FSH and testosterone; males are infertile. Additionally, Tsc22d3-2 KO mice display subtle renal sodium/water handling deficiency but no major immunological defects under unstressed conditions. Cre/loxP conditional KO (Tsc22d3-2), testis histology, TUNEL apoptosis, hormone quantification (FSH, testosterone), renal electrolyte measurement, immune challenges Molecular endocrinology High 22556341
2015 GILZ-deficient mice develop progressive B-cell lymphocytosis with expansion of B220+ cells dependent on increased B-cell survival; decreased B-cell apoptosis in gilz KO mice correlates with increased NF-κB transcriptional activity and Bcl-2 expression. B-cell-specific gilz KO confirms the effect is B-cell intrinsic. Global and B-cell-specific gilz KO mice, flow cytometry, apoptosis assays, NF-κB reporter, Bcl-2 Western blot Blood High 26276664
2012 In alcohol-treated cells, unliganded GR binds GREs in the GILZ proximal promoter (shown by gel mobility shift assay) and transactivates gilz expression independent of glucocorticoids; GR knockout (CRISPR/Cas9) or GILZ depletion (siRNA) diminishes alcohol-mediated suppression of the LPS inflammatory response. Gel mobility shift assay (EMSA) for GR–GRE interaction, GRE deletion/mutation luciferase reporters, CRISPR/Cas9 GR knockout, siRNA GILZ knockdown, GR nuclear translocation, alcohol dehydrogenase inhibitor (fomepizole) Frontiers in immunology Medium 28638383
2017 IBDV VP4 suppresses GILZ K48-linked ubiquitylation, protecting GILZ from degradation and thereby inhibiting IFN-β expression. Mutation of VP4 residue R41G abolishes both VP4's inhibitory effect on IFN-β and on GILZ ubiquitylation. IBDV infection also markedly inhibits endogenous GILZ ubiquitylation. Ubiquitylation assays (K48-linkage specific), VP4 R41G point mutant, IBDV infection of cells, IFN-β reporter assays Immunobiology Medium 29146236
2012 Bacterial toxins YopT and Clostridium difficile toxin B induce GILZ expression in epithelial cells by inactivating Rho GTPases; MAPK activation is required. USF-1 and USF-2 bind a canonical E-box (c-Myc binding site) in the GILZ promoter, which is essential for both basal and toxin-B-induced GILZ transcription. GILZ promoter reporter assays, gel shift analysis (EMSA for USF1/2 binding), USF-1/2 siRNA knockdown, MAPK inhibitors, Yersinia mutant strains, RhoA/RhoB overexpression PloS one Medium 22792400
2023 RBM47-ISGylation (at K329) negatively regulates TSC22D3 mRNA expression; K329R knockin mice with defective RBM47 ISGylation show elevated TSC22D3 and broad immunosuppression. A nanobody-targeted E3 ligase inducing site-specific RBM47 ISGylation in human cells directly inhibits TSC22D3 expression. K329R knockin mice, nanobody-targeted site-specific ISGylation in human cells, TSC22D3 mRNA quantification, LPS-induced lung injury and tumor models Cell death discovery Medium 38036512

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity. Nature medicine 295 31501614
2009 Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 267 19567371
2001 Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ. The Journal of biological chemistry 233 11397794
2002 Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood 226 12393603
2012 Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder. Translational psychiatry 145 22832853
2007 GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling. The Journal of clinical investigation 134 17492054
2005 GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response. Blood 128 16293609
2004 GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. Blood 121 15031210
2007 Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). The Journal of biological chemistry 115 18084007
2003 A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO reports 109 12671681
2014 GILZ promotes production of peripherally induced Treg cells and mediates the crosstalk between glucocorticoids and TGF-β signaling. Cell reports 108 24703841
2006 Glucocorticoid-induced leucine zipper (GILZ)/NF-kappaB interaction: role of GILZ homo-dimerization and C-terminal domain. Nucleic acids research 107 17169985
2015 GILZ as a Mediator of the Anti-Inflammatory Effects of Glucocorticoids. Frontiers in endocrinology 106 26617572
2011 Role of GILZ in immune regulation, glucocorticoid actions and rheumatoid arthritis. Nature reviews. Rheumatology 102 21556028
2004 Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice. Blood 89 15319285
2006 Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ. American journal of physiology. Renal physiology 82 16720863
2003 Mineralocorticoid effects in the kidney: correlation between alphaENaC, GILZ, and Sgk-1 mRNA expression and urinary excretion of Na+ and K+. Journal of the American Society of Nephrology : JASN 79 12707381
2005 Increased GILZ expression in transgenic mice up-regulates Th-2 lymphokines. Blood 76 16204313
2011 Long glucocorticoid-induced leucine zipper (L-GILZ) protein interacts with ras protein pathway and contributes to spermatogenesis control. The Journal of biological chemistry 71 22110132
2010 Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids. The Journal of biological chemistry 56 20124407
2008 Glucocorticoid-induced leucine zipper (GILZ) mediates glucocorticoid action and inhibits inflammatory cytokine-induced COX-2 expression. Journal of cellular biochemistry 56 17910039
2013 LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome. EMBO molecular medicine 55 23495141
2013 GILZ overexpression inhibits endothelial cell adhesive function through regulation of NF-κB and MAPK activity. Journal of immunology (Baltimore, Md. : 1950) 52 23729444
2019 Implicating the Role of GILZ in Glucocorticoid Modulation of T-Cell Activation. Frontiers in immunology 50 31440237
2014 Downregulation of the glucocorticoid-induced leucine zipper (GILZ) promotes vascular inflammation. Atherosclerosis 50 24747114
2015 Lack of glucocorticoid-induced leucine zipper (GILZ) deregulates B-cell survival and results in B-cell lymphocytosis in mice. Blood 47 26276664
2015 GILZ regulates Th17 responses and restrains IL-17-mediated skin inflammation. Journal of autoimmunity 46 26077873
2016 Induction of Glucocorticoid-induced Leucine Zipper (GILZ) Contributes to Anti-inflammatory Effects of the Natural Product Curcumin in Macrophages. The Journal of biological chemistry 43 27629417
2012 Glucocorticoid-induced leucine zipper (GILZ) over-expression in T lymphocytes inhibits inflammation and tissue damage in spinal cord injury. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 40 22125095
2018 GILZ restrains neutrophil activation by inhibiting the MAPK pathway. Journal of leukocyte biology 39 30371949
2012 Estradiol antagonism of glucocorticoid-induced GILZ expression in human uterine epithelial cells and murine uterus. Endocrinology 39 23183181
2011 GILZ inhibits the mTORC2/AKT pathway in BCR-ABL(+) cells. Oncogene 39 21804606
2015 Decreased expression of the glucocorticoid receptor-GILZ pathway in Kupffer cells promotes liver inflammation in obese mice. Journal of hepatology 38 26639395
2014 Development of novel treatment strategies for inflammatory diseases-similarities and divergence between glucocorticoids and GILZ. Frontiers in pharmacology 38 25100999
2012 The glucocorticoid-induced leucine zipper (gilz/Tsc22d3-2) gene locus plays a crucial role in male fertility. Molecular endocrinology (Baltimore, Md.) 38 22556341
2006 Inhibited cell death, NF-kappaB activity and increased IL-10 in TCR-triggered thymocytes of transgenic mice overexpressing the glucocorticoid-induced protein GILZ. International immunopharmacology 38 16714216
2015 Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus. Annals of the rheumatic diseases 34 26612340
2008 Dual regulation of glucocorticoid-induced leucine zipper (GILZ) by the glucocorticoid receptor and the PI3-kinase/AKT pathways in multiple myeloma. The Journal of steroid biochemistry and molecular biology 34 18499442
2018 GILZ-dependent modulation of mTORC1 regulates spermatogonial maintenance. Development (Cambridge, England) 33 30126904
2009 Glucocorticoid-induced leucine zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner. The Journal of biological chemistry 33 20018851
2021 GILZ as a Regulator of Cell Fate and Inflammation. Cells 32 35011684
2013 Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. PloS one 32 23516608
2012 Targeting the side effects of steroid therapy in autoimmune diseases: the role of GILZ. Discovery medicine 32 22369971
2019 Amplified Host Defense by Toll-Like Receptor-Mediated Downregulation of the Glucocorticoid-Induced Leucine Zipper (GILZ) in Macrophages. Frontiers in immunology 31 30723476
2013 Dexamethasone inhibits repair of human airway epithelial cells mediated by glucocorticoid-induced leucine zipper (GILZ). PloS one 31 23573276
2014 L-GILZ binds p53 and MDM2 and suppresses tumor growth through p53 activation in human cancer cells. Cell death and differentiation 30 25168242
2009 The glucocorticoid-induced leucine zipper gene (GILZ) expression decreases after successful treatment of patients with endogenous Cushing's syndrome and may play a role in glucocorticoid-induced osteoporosis. The Journal of clinical endocrinology and metabolism 30 19875485
2011 Medaka osmotic stress transcription factor 1b (Ostf1b/TSC22D3-2) triggers hyperosmotic responses of different ion transporters in medaka gill and human embryonic kidney cells via the JNK signalling pathway. The international journal of biochemistry & cell biology 28 21907305
2014 GILZ: Glitzing up our understanding of the glucocorticoid receptor in psychopathology. Brain research 27 24931768
2013 DC-SCRIPT regulates glucocorticoid receptor function and expression of its target GILZ in dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 27 23440419
2015 Quantitative tissue-specific dynamics of in vivo GILZ mRNA expression and regulation by endogenous and exogenous glucocorticoids. Physiological reports 26 26056061
2014 Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition. The Journal of biological chemistry 26 24860090
2016 Melanoma dormancy in a mouse model is linked to GILZ/FOXO3A-dependent quiescence of disseminated stem-like cells. Scientific reports 25 27465291
2013 Activation of GILZ gene by photoactivated 8-methoxypsoralen: potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 25 24215840
2004 Cell type-specific bidirectional regulation of the glucocorticoid-induced leucine zipper (GILZ) gene by estrogen. The Journal of steroid biochemistry and molecular biology 25 15336700
2019 Overexpression of Gilz Protects Mice Against Lethal Septic Peritonitis. Shock (Augusta, Ga.) 23 30124596
2015 Glucocorticoid-induced leucine zipper (GILZ) in immuno suppression: master regulator or bystander? Oncotarget 23 26498359
2012 Glucocorticoid-induced leucine zipper (GILZ) antagonizes TNF-α inhibition of mesenchymal stem cell osteogenic differentiation. PloS one 23 22396737
2012 The Glucocorticoid-induced leucine zipper (GILZ) Is essential for spermatogonial survival and spermatogenesis. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 23 22571926
2007 Localization of glucocorticoid-induced leucine zipper (GILZ) expressing neurons in the central nervous system and its relationship to the stress response. Brain research 23 17574218
2020 Overexpression of GILZ in macrophages limits systemic inflammation while increasing bacterial clearance in sepsis in mice. European journal of immunology 22 31840802
2018 Temporal dynamics of cortisol-associated changes in mRNA expression of glucocorticoid responsive genes FKBP5, GILZ, SDPR, PER1, PER2 and PER3 in healthy humans. Psychoneuroendocrinology 22 30522007
2019 Could GILZ Be the Answer to Glucocorticoid Toxicity in Lupus? Frontiers in immunology 20 31379872
2019 Glucocorticoids and Glucocorticoid-Induced-Leucine-Zipper (GILZ) in Psoriasis. Frontiers in immunology 20 31572404
2020 Glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced Müller glial galectin-1 expression via HIF-1α destabilization. Journal of cellular and molecular medicine 19 32150332
1996 hDIP--a potential transcriptional regulator related to murine TSC-22 and Drosophila shortsighted (shs)--is expressed in a large number of human tissues. Biochimica et biophysica acta 19 8982256
2019 Cholesterol Starvation and Hypoxia Activate the FVII Gene via the SREBP1-GILZ Pathway in Ovarian Cancer Cells to Produce Procoagulant Microvesicles. Thrombosis and haemostasis 18 31055798
2010 Glucocorticoid-induced activation of caspase-8 protects the glucocorticoid-induced protein Gilz from proteasomal degradation and induces its binding to SUMO-1 in murine thymocytes. Cell death and differentiation 18 20671745
2007 Notch signaling links interactions between the C/EBP homolog slow border cells and the GILZ homolog bunched during cell migration. Developmental biology 17 17383627
2016 Overexpression of Glucocorticoid-induced Leucine Zipper (GILZ) increases susceptibility to Imiquimod-induced psoriasis and involves cutaneous activation of TGF-β1. Scientific reports 16 27934944
2013 Zebrafish transforming growth factor-β-stimulated clone 22 domain 3 (TSC22D3) plays critical roles in Bmp-dependent dorsoventral patterning via two deubiquitylating enzymes Usp15 and Otud4. Biochimica et biophysica acta 16 23665588
2022 GILZ regulates type I interferon release and sequesters STAT1. Journal of autoimmunity 15 35810690
2016 Low expression of the GILZ may contribute to adipose inflammation and altered adipokine production in human obesity. Journal of lipid research 15 27178044
2023 Association of GILZ with MUC2, TLR2, and TLR4 in Inflammatory Bowel Disease. International journal of molecular sciences 14 36768553
2019 Modeling Corticosteroid Pharmacokinetics and Pharmacodynamics, Part III: Estrous Cycle and Estrogen Receptor-Dependent Antagonism of Glucocorticoid-Induced Leucine Zipper (GILZ) Enhancement by Corticosteroids. The Journal of pharmacology and experimental therapeutics 14 31197018
2018 Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and Th17 Cell Interplay. Theranostics 14 29344311
2017 Infectious bursal disease virus protein VP4 suppresses type I interferon expression via inhibiting K48-linked ubiquitylation of glucocorticoid-induced leucine zipper (GILZ). Immunobiology 14 29146236
2016 GILZ overexpression attenuates endoplasmic reticulum stress-mediated cell death via the activation of mitochondrial oxidative phosphorylation. Biochemical and biophysical research communications 14 27416758
2014 Recombinant long-glucocorticoid-induced leucine zipper (L-GILZ) protein restores the control of proliferation in gilz KO spermatogonia. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 14 24993177
2014 Glucocorticoid-induced leucine zipper (GILZ) controls inflammation and tissue damage after spinal cord injury. CNS neuroscience & therapeutics 14 25146427
2019 The testicular soma of Tsc22d3 knockout mice supports spermatogenesis and germline transmission from spermatogonial stem cell lines upon transplantation. Genesis (New York, N.Y. : 2000) 13 31001916
2016 Glucocorticoid-induced leucine zipper (GILZ) is involved in glucocorticoid-induced and mineralocorticoid-induced leptin production by osteoarthritis synovial fibroblasts. Arthritis research & therapy 13 27716396
2015 A focused Real Time PCR strategy to determine GILZ expression in mouse tissues. Results in immunology 13 26697291
2010 [GILZ (glucocorticoid-induced leucine zipper), a mediator of the anti-inflammatory and immunosuppressive activity of glucocorticoids]. Annali di igiene : medicina preventiva e di comunita 13 20701225
2007 IL-2 induces and altered CD4/CD8 ratio of splenic T lymphocytes from transgenic mice overexpressing the glucocorticoid-induced protein GILZ. Journal of chemotherapy (Florence, Italy) 13 18073156
2022 Type 1 interferon suppresses expression and glucocorticoid induction of glucocorticoid-induced leucine zipper (GILZ). Frontiers in immunology 12 36505447
2022 SOCS3 Attenuates Dexamethasone-Induced M2 Polarization by Down-Regulation of GILZ via ROS- and p38 MAPK-Dependent Pathways. Immune network 11 36081527
2021 GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus. Frontiers in immunology 11 33889157
2017 Metabolic rewiring in cancer cells overexpressing the glucocorticoid-induced leucine zipper protein (GILZ): Activation of mitochondrial oxidative phosphorylation and sensitization to oxidative cell death induced by mitochondrial targeted drugs. The international journal of biochemistry & cell biology 11 28259749
2017 Role of glucocorticoid-induced leucine zipper (GILZ) in inflammatory bone loss. PloS one 11 28771604
2016 Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity. Annals of intensive care 11 27807817
2013 Expression of glucocorticoid-induced leucine zipper (GILZ) in cardiomyocytes. Cardiovascular toxicology 11 23090754
2011 High TSC22D3 and low GBP1 expression in the liver is a risk factor for early recurrence of hepatocellular carcinoma. Experimental and therapeutic medicine 11 22977521
2007 Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone. PPAR research 11 18309369
2017 The role of GILZ in modulation of adaptive immunity in a murine model of myocardial infarction. Experimental and molecular pathology 10 28499885
2010 Role of glucocorticoid-induced leucine zipper (GILZ) expression by dendritic cells in tolerance induction. Transplantation proceedings 10 20970683
2018 Clock represses preadipocytes adipogenesis via GILZ. Journal of cellular physiology 9 29278648
2017 Non-canonical Glucocorticoid Receptor Transactivation of gilz by Alcohol Suppresses Cell Inflammatory Response. Frontiers in immunology 9 28638383
2023 Dynamic RBM47 ISGylation confers broad immunoprotection against lung injury and tumorigenesis via TSC22D3 downregulation. Cell death discovery 8 38036512
2012 Yersinia enterocolitica YopT and Clostridium difficile toxin B induce expression of GILZ in epithelial cells. PloS one 8 22792400

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