Affinage

TSC22D1

TSC22 domain family protein 1 · UniProt Q15714

Length
1073 aa
Mass
109.7 kDa
Annotated
2026-04-28
56 papers in source corpus 26 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TSC22D1 encodes a leucine zipper transcription factor that functions as a context-dependent regulator of cell growth, apoptosis, and TGF-β signaling through isoform-specific mechanisms. The short isoform (TSC22D1-2) resides in the cytoplasm and translocates to the nucleus upon apoptotic or DNA-damage stimuli, where it promotes cell death by stabilizing p53 against ubiquitination, inhibiting GILZ transcription, and enhancing TGF-β signaling by disrupting Smad7/Smurf-mediated degradation of TβRI; it also cooperates with Tfe3 at E-box elements and with Smad3/4 to drive target gene expression (PMID:21791611, PMID:22870275, PMID:26752201, PMID:20713358, PMID:15881652). The long isoform (TSC22D1-1) is constitutively nuclear, promotes cell proliferation, and is selectively degraded by the proteasome during oncogene-induced senescence, establishing opposing isoform roles in growth control (PMID:21448135, PMID:19745830, PMID:30912127). TSC22D1 protein and mRNA levels are regulated post-transcriptionally through 3′-UTR AU-rich element-mediated mRNA stabilization downstream of TGF-β, m6A/YTHDF1-dependent mRNA degradation, MEX3D-mediated mRNA decay, and fortilin-dependent protein destabilization (PMID:12767908, PMID:41472023, PMID:35513372, PMID:18325344).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    The question of where TSC-22 acts was addressed by showing it is a cytoplasmic protein that translocates to the nucleus upon apoptosis, establishing stimulus-dependent nucleocytoplasmic shuttling as central to its function.

    Evidence Live-cell fluorescence microscopy of TSC-22-GFP fusion and GAL4 transcriptional reporter assays in mammalian and yeast cells

    PMID:11095965

    Open questions at the time
    • Mechanism of nuclear translocation signal not identified
    • Endogenous protein localization not confirmed
  2. 2002 Medium

    The structural basis of TSC-22 growth suppression and radiosensitization was mapped: the leucine zipper domain is the minimal growth-inhibitory unit, and cytoplasm-to-nucleus translocation is required for radiation-induced apoptosis, establishing domain-function relationships.

    Evidence Domain-deletion constructs with anchorage-independent growth and radiation sensitivity assays in mammalian cells

    PMID:11836610 PMID:11944908

    Open questions at the time
    • Nuclear targets mediating radiosensitization unknown
    • No structural data for TSC-22 leucine zipper
  3. 2002 Medium

    TSC-22 was placed downstream of both TGF-β and PPARγ as a growth-inhibitory effector that induces p21, with dominant-negative TSC-22 blocking this response, establishing it as a convergent node for antiproliferative signaling.

    Evidence Wild-type and dominant-negative TSC-22 transfection with growth assays and p21 expression in intestinal epithelial cells

    PMID:12468551

    Open questions at the time
    • Direct transcriptional targets not identified genome-wide
    • Whether TSC-22 directly binds p21 promoter not tested
  4. 2003 Medium

    The mechanism by which TGF-β elevates TSC-22 was shown to be post-transcriptional mRNA stabilization via 3′-UTR AUUUA elements rather than transcriptional activation, identifying a novel regulatory layer.

    Evidence Promoter reporter, RNA gel shift, and mRNA stability assays with heterologous reporter constructs

    PMID:12767908

    Open questions at the time
    • Identity of the 40-kDa destabilizing protein not determined at this time
    • In vivo relevance of mRNA stabilization not tested
  5. 2005 Medium

    TSC-22 was connected to the Smad transcriptional machinery by demonstrating direct binding to Smad3 and Smad4 and enhancement of TGF-β-dependent reporter activity, explaining how it amplifies TGF-β signaling.

    Evidence Co-immunoprecipitation and transcriptional reporter assays in erythroid differentiation system

    PMID:15881652

    Open questions at the time
    • Whether TSC-22–Smad interaction is direct or bridged not resolved
    • Genome-wide target overlap with Smads not mapped
  6. 2008 Medium

    Post-translational regulation of TSC-22 was identified: fortilin binds TSC-22 and promotes its degradation, counteracting TSC-22-induced apoptosis, establishing a protein-level control mechanism.

    Evidence Yeast two-hybrid, co-immunoprecipitation, and apoptosis rescue by fortilin overexpression/knockdown in ovarian carcinoma cells

    PMID:18325344

    Open questions at the time
    • Degradation pathway (proteasomal vs. lysosomal) not determined
    • Fortilin binding site on TSC-22 not mapped
  7. 2009 Medium

    The opposing-isoform paradigm was established: the short isoform promotes apoptosis during mammary involution while the long isoform suppresses TGF-β-induced death and enhances proliferation, resolving contradictory reports of growth-suppressive and proliferative activities.

    Evidence Isoform-specific overexpression and knockdown with cell death and proliferation assays in mammary epithelial cells

    PMID:19745830

    Open questions at the time
    • Whether opposing isoform functions reflect distinct promoter usage or alternative splicing not resolved
    • Isoform-specific interactomes not compared
  8. 2010 High

    The post-transcriptional regulation was refined: TGF-β induces miR-216a to downregulate the RNA-binding protein Ybx1, relieving Ybx1-mediated TSC-22 mRNA destabilization; elevated TSC-22 then co-occupies E-box enhancers with Tfe3 to drive Col1a2 transcription, linking mRNA regulation to a specific chromatin target.

    Evidence ChIP, Co-IP, RNA-IP, miRNA mimic/inhibitor, shRNA knockdown, and luciferase reporters in renal mesangial cells

    PMID:20713358

    Open questions at the time
    • Whether Tfe3–TSC-22 cooperation is a general mechanism beyond Col1a2 is unknown
    • Direct DNA-binding activity of TSC-22 itself not demonstrated
  9. 2011 High

    TSC-22 was shown to enhance TGF-β receptor signaling at the receptor level by binding TβRI and Smad7 in mutually exclusive complexes, disrupting Smad7/Smurf-mediated ubiquitination and degradation of TβRI, explaining how TSC-22 amplifies pathway activation.

    Evidence Reciprocal co-immunoprecipitation, ubiquitination assays, Smad2/3 phosphorylation, and fibrotic gene expression in rat cardiac fibrosis model

    PMID:21791611

    Open questions at the time
    • Whether TSC-22 binds other Smad pathway ubiquitin ligases not tested
    • Structural basis of mutual exclusivity between TβRI and Smad7 binding not resolved
  10. 2011 High

    The opposing-isoform model was extended to oncogene-induced senescence: the short isoform is upregulated downstream of C/EBPβ and promotes senescence via p15(INK4B), while the long isoform is proteasomally degraded during OIS, confirming isoform-specific regulation in a cancer-relevant context.

    Evidence Isoform-specific shRNA, overexpression, proteasome inhibitor treatment, and C/EBPβ epistasis in BRAF(E600) OIS system

    PMID:21448135

    Open questions at the time
    • Whether proteasomal degradation of long isoform during OIS involves a specific E3 ligase not identified
    • Contribution of TSC22D1 to in vivo tumor suppression not tested
  11. 2012 Medium

    TSC-22 was established as a stabilizer of p53 by directly binding p53 residues 100–200 and inhibiting HDM2- and HPV E6-mediated poly-ubiquitination, linking TSC-22 to a major tumor suppressor pathway.

    Evidence Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, and xenograft mouse model

    PMID:22870275

    Open questions at the time
    • Whether TSC-22 competes directly with HDM2 for the same p53 binding surface not determined
    • In vivo p53 stabilization in TSC-22 knockout not tested
  12. 2016 Medium

    TSC-22 was shown to promote apoptosis in T-lymphocytes by transcriptionally repressing GILZ, thereby de-repressing BIM and activating the intrinsic apoptotic cascade, identifying a specific transcriptional target in immune cell death.

    Evidence Stable overexpression, caspase and BIM assays, and GILZ epistasis in IL-2-deprived T-lymphocytes

    PMID:26752201

    Open questions at the time
    • Whether TSC-22 directly binds the GILZ promoter not shown
    • Physiological relevance in T-cell homeostasis in vivo not validated
  13. 2021 Medium

    Isoform-specific localization was mapped at the organelle level: the short isoform localizes predominantly to mitochondria and translocates to the nucleus after DNA damage, where it binds Histone H1 and nucleostemin (GNL3), providing compartment-specific interactors.

    Evidence Fluorescence microscopy of tagged isoforms, subcellular fractionation, pull-down and co-immunoprecipitation with mass spectrometry

    PMID:34681573

    Open questions at the time
    • Functional consequence of Histone H1 and GNL3 interactions not determined
    • Mitochondrial function of short isoform unclear
  14. 2022 Medium

    An additional layer of mRNA-level regulation was revealed: MEX3D directly binds TSC22D1 mRNA and promotes its degradation in cervical cancer cells.

    Evidence RNA pull-down, RNA immunoprecipitation, and mRNA stability assays

    PMID:35513372

    Open questions at the time
    • Binding site on TSC22D1 mRNA not mapped
    • Physiological context of MEX3D regulation not established
  15. 2025 Medium

    m6A epitranscriptomic regulation of TSC22D1 was identified: YTHDF1 binds m6A-modified TSC22D1 mRNA and promotes its degradation, adding an RNA modification-dependent control layer distinct from AU-rich element regulation.

    Evidence MeRIP-seq, YTHDF1 knockdown, and mRNA stability assays in EBV-infection context

    PMID:41472023

    Open questions at the time
    • Specific m6A sites on TSC22D1 mRNA not mapped
    • Whether m6A regulation operates outside the EBV context not tested
  16. 2025 Medium

    TSC22D1 was connected to pancreatic beta cell identity: TSC22D1 interacts with FoxO1, and its depletion enhances beta cell identity gene expression and glucose-stimulated insulin secretion, revealing a repressive role in beta cell function.

    Evidence siRNA knockdown in INS-1E cells, co-immunoprecipitation, interactome mass spectrometry, RNA-seq, insulin secretion assay

    PMID:40679946

    Open questions at the time
    • Whether TSC22D1–FoxO1 interaction is direct or part of a larger complex not resolved
    • In vivo beta cell phenotype of TSC22D1 loss not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include whether TSC22D1 has intrinsic DNA-binding activity or functions exclusively through protein–protein interactions at chromatin, the structural basis for isoform-specific functions, the identity of E3 ligases controlling long-isoform degradation, and the physiological importance of the mitochondrial pool of the short isoform.
  • No direct DNA-binding data for any TSC22D1 isoform
  • No crystal or cryo-EM structure
  • Long isoform-specific E3 ligase unknown
  • Mitochondrial function not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-5357801 Programmed Cell Death 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3
Partners
FOXO1NRBP1SMAD3SMAD7TCEAL7TFE3TGFBR1TP53

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 TSC-22 facilitates TGF-β signaling by interacting with TGF-β type I receptor (TβRI) and Smad7 in mutually exclusive ways, disrupting the Smad7/Smurf complex association with TβRI and thereby preventing ubiquitination and degradation of the receptor, leading to enhanced Smad2/3 phosphorylation and transcriptional responsiveness. This promotes cardiac myofibroblast differentiation. Co-immunoprecipitation, siRNA knockdown, Smad2/3 phosphorylation assays, fibrotic gene expression analysis in isoproterenol-induced rat myocardial fibrosis model Molecular and cellular biology High 21791611
2005 Tsc-22 binds to Smad3 and Smad4 and modulates their transcriptional activity to enhance TGF-β-dependent signaling, and promotes erythroid cell differentiation. Co-immunoprecipitation, transcriptional reporter assays, cell differentiation assays Molecular and cellular biochemistry Medium 15881652
2010 TGF-β up-regulates TSC-22 protein post-transcriptionally by reducing Ybx1-mediated ribonucleoprotein complex formation with TSC-22 mRNA (through miR-216a-mediated Ybx1 down-regulation); elevated TSC-22 then interacts with Tfe3 at E-box enhancers of the Col1a2 gene to drive collagen expression in renal mesangial cells. ChIP, Co-immunoprecipitation, RNA immunoprecipitation, miRNA mimic/inhibitor treatment, shRNA knockdown, luciferase reporter assays The Journal of biological chemistry High 20713358
2003 TGF-β1 up-regulates TSC-22 mRNA through mRNA stabilization rather than transcriptional activation; three AUUUA (Shaw-Kamens) sequences in the TSC-22 mRNA 3'-UTR act as destabilizing elements, and TGF-β1 reduces binding of a 40 kDa protein to this element to stabilize the mRNA. Promoter luciferase reporter assay, RNA-binding protein gel shift assay, mRNA stability assay with heterologous reporter Biochemical and biophysical research communications Medium 12767908
2000 TSC-22-GFP fusion protein localizes to the cytoplasm in living cells but translocates to the nucleus upon induction of apoptosis; nuclear TSC-22 shows transcription-regulatory activity in a cell-type-dependent manner. Live-cell fluorescence microscopy of TSC-22-GFP fusion protein, GAL4 fusion reporter assay in yeast and mammalian cells Biochemical and biophysical research communications Medium 11095965
2002 Cytoplasmic localization of TSC-22 and its translocation from cytoplasm to nucleus is required for radiation-induced apoptosis; the nuclear export signal-containing full-length TSC-22 in the cytoplasm markedly enhances radiation sensitivity, while nuclear-restricted TSC-22 (NLS-TSC-22LZ) has minimal effect. Stable transfection with domain-deletion constructs (TSC-22FL, TSC-22LZ, NLS-TSC-22LZ), radiation sensitivity assays, fluorescence microscopy Biochemical and biophysical research communications Medium 11944908
2002 The leucine zipper domain of TSC-22 is the active domain responsible for inhibiting anchorage-independent growth; the full-length TSC-22 (cytoplasmic) had weaker effects than leucine zipper constructs expressed in both cytoplasm and nucleus. Stable transfection with domain-deletion constructs, anchorage-independent colony formation assay Oncology reports Medium 11836610
2012 TSC-22 physically interacts with the region between amino acids 100–200 of p53 and inhibits HDM2- and HPV E6-mediated poly-ubiquitination of p53, thereby protecting p53 from proteasomal degradation and activating p21Waf1/Cip1 and PUMA expression. TSC-22 knockdown enhanced p53 poly-ubiquitination. Co-immunoprecipitation, siRNA knockdown, ubiquitination assay, xenograft mouse model PloS one Medium 22870275
2011 TSC22D1 exists as two isoforms (short and long) with opposing functions in BRAF(E600)-induced oncogene-induced senescence (OIS): the short isoform is upregulated and promotes senescence, while the large isoform is degraded by the proteasome. Both form complexes with their dimerization partner THG1 (TSC22 homologue gene 1). TSC22D1 acts as a downstream effector of C/EBPβ and controls p15(INK4B) and inflammatory factors during OIS. Gene expression profiling, selective isoform depletion by shRNA, overexpression of large variant, proteasome inhibitor treatment, epistasis with C/EBPβ The EMBO journal High 21448135
2009 TSC-22D1 isoform 2 (short) promotes apoptosis during mammary gland involution, while isoform 1 (long) suppresses TGF-β-induced cell death and enhances proliferation; these two isoforms have opposing roles in mammary epithelial cell survival. Overexpression and knockdown in mammary epithelial cell lines, cell death and proliferation assays, protein detection in mammary gland tissue Cell death and differentiation Medium 19745830
2008 A C-terminal 86 amino acid fragment of TSC-22 (Tsc22(86)) suppresses Bax-induced apoptosis in yeast independently of the leucine zipper motif; a conserved 16-residue sequence within the TSC22 domain is necessary for this antiapoptotic function. Yeast two-hybrid screen, genome-wide two-hybrid, deletion mutagenesis, functional apoptosis suppression assay in yeast FEMS yeast research Medium 18355271
2008 Fortilin interacts with TSC-22 (identified by yeast two-hybrid) and promotes TSC-22 degradation; overexpression of fortilin reverses TSC-22-mediated apoptosis in ovarian carcinoma cells, while fortilin siRNA increases apoptosis. Yeast two-hybrid, Co-immunoprecipitation, siRNA knockdown, apoptosis assay FEBS letters Medium 18325344
2017 TSC-22 directly interacts with the intracellular tyrosine kinase insert domain (residues 539–749) of CSF-1R, blocking AKT and ERK signaling and suppressing NF-κB transcriptional activity; overexpression of TSC-22 decreases CSF-1R protein levels and suppresses cervical cancer cell proliferation and motility. Co-immunoprecipitation, domain mapping, AKT/ERK/NF-κB signaling assays, xenograft mouse model Oncotarget Medium 29228668
2002 TSC-22 is a downstream effector of both PPARγ and TGF-β pathways in intestinal epithelial cells; expression of TSC-22 reduces cell growth and increases p21 levels, while a dominant-negative TSC-22 (with both repressor domains deleted) reverses growth inhibition and p21 induction caused by PPARγ or TGF-β activation. Transfection with wild-type and dominant-negative TSC-22, growth assays, p21 expression analysis, pathway epistasis The Journal of biological chemistry Medium 12468551
2004 TSC-22 (XTSC-22) in Xenopus laevis is required for cell migration during gastrulation; morpholino knockdown causes defective blastopore closure due to impaired ectoderm cell migration and increased cell division, which is rescued by co-injection of p27Xic1 (a cyclin/Cdk inhibitor), placing TSC-22 upstream of cell-cycle regulation. Antisense morpholino knockdown, cell lineage tracing, whole-mount in situ hybridization, mRNA rescue, p27Xic1 epistasis Development, growth & differentiation Medium 15610143
2007 TSC-22 targeted disruption in mice enhances proliferation and in vivo repopulation efficiency of hematopoietic precursor cells (HPCs), demonstrating a role for TSC-22 in regulating HPC function. Targeted gene disruption (knockout mouse), in vivo HPC repopulation assay Blood Medium 19329776
2016 TSC-22 promotes IL-2-deprivation-induced apoptosis in T-lymphocytes by inhibiting GILZ mRNA transcription, preventing GILZ protein induction and thereby increasing BIM expression and caspase-9/-3 activation. Stable transfection, apoptosis assays (caspase activity, BIM expression), mRNA quantification, functional epistasis between TSC-22 and GILZ Journal of cellular biochemistry Medium 26752201
2010 TSC22D1 is required for TGF-β1- and PDGF-BB-induced CNP (C-type natriuretic peptide) expression in human vascular smooth muscle cells; siRNA-mediated suppression of TSC22D1 by ~90% reduces TGF-β- and PDGF-stimulated CNP expression by 45–65%, establishing TSC22D1 as an enhancer of CNP transcription. siRNA knockdown, qRT-PCR, correlation of TSC22D1 and CNP mRNA induction American journal of physiology. Heart and circulatory physiology Medium 20802130
2021 TSC22D1 family proteins have distinct intracellular localizations: TSC22D1-1 (long isoform) is predominantly nuclear, TSC-22 (TSC22D1-2, short) is cytoplasmic (mainly mitochondrial) and translocates to the nucleus after DNA damage, and TSC22D1-3 is in both compartments. Binding partners identified by mass spectrometry include Histone H1 (binding TSC22D1-2 and TSC22D1-3 in the nucleus) and GNL3/nucleostemin (binding TSC22D1-2 in the nucleus). Fluorescence microscopy of tagged proteins, subcellular fractionation, in vitro pull-down and in vivo co-immunoprecipitation followed by mass spectrometry International journal of molecular sciences Medium 34681573
2019 TSC22D4–TSC22D1 short isoform heterodimers promote exit from cell proliferation and cell-cycle, whereas TSC22D1 long isoform is required for cell proliferation independently of TSC22D4; silencing specific isoforms alters cell-cycle progression in medulloblastoma cells. siRNA knockdown of specific isoforms, cell-cycle analysis, proliferation assays in DAOY medulloblastoma cells Journal of cellular physiology Medium 30912127
2022 MEX3D (an RNA-binding protein) directly binds TSC22D1 mRNA and promotes its degradation, reducing TSC22D1 levels in cervical cancer cells. RNA pull-down, RNA immunoprecipitation, mRNA stability assay Cell death discovery Medium 35513372
2025 TSC22D1 interacts with FoxO1 in pancreatic beta cells in a reciprocal regulatory manner; TSC22D1 depletion enhances beta cell identity gene expression (Ins1, Ins2, Pdx1, Slc2a2, Nkx6.1) and glucose-stimulated insulin secretion. Interactome analysis implicates TSC22D1 in mRNA processing, ribonucleoprotein complex biogenesis, and Golgi vesicle transport in beta cells. siRNA knockdown in INS-1E cells, co-immunoprecipitation, interactome mass spectrometry, RNA-seq, glucose-stimulated insulin secretion assay The FEBS journal Medium 40679946
2025 TSC22D1 drives liver sinusoidal endothelial cell (LSEC) dysfunction and macrophage M1 polarization via the TWEAK/FN14 signaling pathway; TSC22D1 promotes endothelial-mesenchymal transition (EndMT) and microvascularization in LSECs, leading to pro-inflammatory cytokine secretion and M1 polarization. AAV8-shRNA inhibition of TSC22D1 reduced NAFLD progression in vivo. Single-cell RNA sequencing, TSC22D1 overexpression in LSECs, TWEAK inhibition, flow cytometry, ELISA, qPCR, in vivo AAV8-shRNA knockdown in NAFLD mice World journal of gastroenterology Medium 40901684
2025 TSC22D1.1 (long isoform) localizes to WNK bodies (cytoplasmic biomolecular condensates) in the distal convoluted tubule and acts as a positive modulator of WNK4 activity, promoting NCC phosphorylation and sodium reabsorption in the kidney. TSC22D1 interacts with NRBP1 within this complex via RΦ-motif/CCT domain interaction. Fluorescence localization in DCT, HEK293 cell WNK4 activity assays with TSC22D1.1 overexpression, NRBP1 DCT-specific knockout mice, NCC phosphorylation assays bioRxivpreprint Medium
2024 TSC22D1 contains an RΦ-motif (R-F-x-V/I) that interacts with the CCT-like domain of the pseudokinase NRBP1 and the CCT domains of OSR1/SPAK, connecting TSC22D1 to the WNK-OSR1/SPAK ion homeostasis signaling pathway. Motif prediction, biochemical binding assays, AlphaFold-3 structural modeling, immunoprecipitation/mass spectrometry validation bioRxivpreprint Low
2011 TSC-22 acts as a suppressor of Gadd45b expression; siRNA-mediated knockdown of Tsc-22 in murine liver cells increases Gadd45b gene and protein expression, and oxazepam treatment decreases Tsc-22 with reciprocal increase in Gadd45b. siRNA knockdown, qRT-PCR, Western blot, chemical treatment (oxazepam) Toxicological sciences Low 17533171
2022 TSC-22 directly interacts with BRD7 and potentiates BRD7-mediated inactivation of the ERK signaling pathway in ovarian cancer cells. Co-immunoprecipitation, ERK pathway activity assays, overexpression Development & reproduction Low 36285148
2025 EBV infection reduces m6A methylation of TSC22D1 mRNA; YTHDF1 (an m6A reader) binds TSC22D1 mRNA and promotes its m6A-dependent degradation; YTHDF1 knockdown increases TSC22D1 mRNA stability and expression. MeRIP-seq, YTHDF1 knockdown, mRNA stability assay Microorganisms Medium 41472023

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells. The Journal of biological chemistry 148 20713358
1998 Down-regulation of TSC-22 (transforming growth factor beta-stimulated clone 22) markedly enhances the growth of a human salivary gland cancer cell line in vitro and in vivo. Cancer research 78 9458104
2002 Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. The Journal of biological chemistry 62 12468551
1998 Induction of TSC-22 by treatment with a new anti-cancer drug, vesnarinone, in a human salivary gland cancer cell. British journal of cancer 53 9459148
2006 Specific TSC22 domain transcripts are hypertonically induced and alternatively spliced to protect mouse kidney cells during osmotic stress. The FEBS journal 52 17147695
1997 The Drosophila bunched gene is a homologue of the growth factor stimulated mammalian TSC-22 sequence and is required during oogenesis. Mechanisms of development 50 9256356
2011 TSC-22 promotes transforming growth factor β-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity. Molecular and cellular biology 49 21791611
2005 Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation. Molecular and cellular biochemistry 47 15881652
2000 Over-expression of TSC-22 (TGF-beta stimulated clone-22) markedly enhances 5-fluorouracil-induced apoptosis in a human salivary gland cancer cell line. Laboratory investigation; a journal of technical methods and pathology 44 10879745
2000 Nuclear translocation of TSC-22 (TGF-beta-stimulated clone-22) concomitant with apoptosis: TSC-22 as a putative transcriptional regulator. Biochemical and biophysical research communications 41 11095965
2003 Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors. Journal of surgical oncology 39 12501169
2011 Identification of fat4 and tsc22d1 as novel candidate genes for spontaneous pulmonary adenomas. Cancer research 34 21764761
2009 TSC-22 contributes to hematopoietic precursor cell proliferation and repopulation and is epigenetically silenced in large granular lymphocyte leukemia. Blood 34 19329776
1999 Dynamic expression of TSC-22 at sites of epithelial-mesenchymal interactions during mouse development. Mechanisms of development 31 10473130
2008 A TSC22-like motif defines a novel antiapoptotic protein family. FEMS yeast research 30 18355271
2006 Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation. Biochimica et biophysica acta 30 17174532
2000 Expression of TGF-beta stimulated clone-22 (TSC-22) in mouse development and TGF-beta signalling. Developmental dynamics : an official publication of the American Association of Anatomists 28 10906776
2012 Crucial role of TSC-22 in preventing the proteasomal degradation of p53 in cervical cancer. PloS one 27 22870275
2011 Antagonistic TSC22D1 variants control BRAF(E600)-induced senescence. The EMBO journal 26 21448135
2008 TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer. Breast cancer research and treatment 25 18299979
2008 Interaction between fortilin and transforming growth factor-beta stimulated clone-22 (TSC-22) prevents apoptosis via the destabilization of TSC-22. FEBS letters 24 18325344
2007 TGF-beta1 and TSC-22 gene polymorphisms and susceptibility to microvascular complications in type 2 diabetes. Nephron. Physiology 24 17622752
2008 Bunched, the Drosophila homolog of the mammalian tumor suppressor TSC-22, promotes cellular growth. BMC developmental biology 23 18226226
2008 The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation, and survival. Proceedings of the National Academy of Sciences of the United States of America 23 18375761
2004 TSC-22 (TGF-beta stimulated clone-22): a novel molecular target for differentiation-inducing therapy in salivary gland cancer. Current cancer drug targets 23 15379637
2002 Cytoplasmic TSC-22 (transforming growth factor-beta-stimulated clone-22) markedly enhances the radiation sensitivity of salivary gland cancer cells. Biochemical and biophysical research communications 22 11944908
2007 Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD. Leukemia 21 17690703
2004 Role of TSC-22 during early embryogenesis in Xenopus laevis. Development, growth & differentiation 21 15610143
2003 Posttranscriptional regulation of TSC-22 (TGF-beta-stimulated clone-22) gene by TGF-beta 1. Biochemical and biophysical research communications 21 12767908
2002 Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather tract. Developmental dynamics : an official publication of the American Association of Anatomists 21 11803572
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
2022 RNA-binding protein MEX3D promotes cervical carcinoma tumorigenesis by destabilizing TSC22D1 mRNA. Cell death discovery 17 35513372
2007 The putative tumor suppressor Tsc-22 is downregulated early in chemically induced hepatocarcinogenesis and may be a suppressor of Gadd45b. Toxicological sciences : an official journal of the Society of Toxicology 16 17533171
2019 The interplay between TGF-β-stimulated TSC22 domain family proteins regulates cell-cycle dynamics in medulloblastoma cells. Journal of cellular physiology 15 30912127
2010 Transforming growth factor-beta1 regulation of C-type natriuretic peptide expression in human vascular smooth muscle cells: dependence on TSC22D1. American journal of physiology. Heart and circulatory physiology 15 20802130
2009 TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival. Cell death and differentiation 14 19745830
2017 TSC-22 inhibits CSF-1R function and induces apoptosis in cervical cancer. Oncotarget 11 29228668
2008 Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The Journal of dermatology 10 18181769
2005 Patterns of expression of TSC-22 protein in astrocytic gliomas. Experimental oncology 10 16404353
2002 Leucine zipper structure of TSC-22 (TGF-beta stimulated clone-22) markedly inhibits the anchorage-independent growth of salivary gland cancer cells. Oncology reports 9 11836610
2021 Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry. International journal of molecular sciences 8 34681573
2016 Overexpression of TSC-22 (transforming growth factor- β-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice. Oncotarget 8 26872059
2008 Expression and cellular localization of TSC-22 in normal salivary glands and salivary gland tumors: implications for tumor cell differentiation. Oncology reports 8 18288391
2003 The role of the TSC-22 (-396) A/G variant in the development of diabetic nephropathy. Diabetes research and clinical practice 7 12757981
2011 Regulation of TGF-β signaling by PKC depends on Tsc-22 inducibility. Molecular and cellular biochemistry 6 21881999
2018 Low levels of TSC22 enhance tumorigenesis by inducing cell proliferation in colorectal cancer. Biochemical and biophysical research communications 5 29481799
2016 TSC-22 Promotes Interleukin-2-Deprivation Induced Apoptosis in T-Lymphocytes. Journal of cellular biochemistry 5 26752201
2001 Human TSC-22 gene: no association with type 2 diabetes. Internal medicine (Tokyo, Japan) 3 11688842
2025 TSC22D1 is a newly identified inhibitor of insulin secretion in pancreatic beta cells. The FEBS journal 2 40679946
2019 Generation of non-standard macrocyclic peptides specifically binding TSC-22 homologous gene-1. Biochemical and biophysical research communications 2 31227214
2011 [Progress of TSC-22 gene research]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2 21873781
2025 TSC22D1 promotes liver sinusoidal endothelial cell dysfunction and induces macrophage M1 polarization in non-alcoholic fatty liver disease. World journal of gastroenterology 1 40901684
2022 Transforming Stimulated Clone 22 (TSC-22) Interacts Directly with Bromodomain-Containing Protein 7 (BRD7) to Enhance the Inhibition of Extracellular Signal-Regulate Kinase (ERK) Pathway in Ovarian Cancer. Development & reproduction 1 36285148
2021 FGFR2-TSC22D1, a novel FGFR2 fusion gene identified in a patient with colorectal cancer: A case report. World journal of clinical cases 1 34447836
2025 TSC22 domain family member 3 links natural killer cells to CD8+ T cell-mediated drug hypersensitivity. Signal transduction and targeted therapy 0 40544157
2025 Epstein-Barr Virus Promotes Gastric Cancer Progression by Modulating m6A-Dependent YTHDF1-TSC22D1 Axis. Microorganisms 0 41472023