Affinage

TSC22D1

TSC22 domain family protein 1 · UniProt Q15714

Length
1073 aa
Mass
109.7 kDa
Annotated
2026-06-10
56 papers in source corpus 32 papers cited in narrative 33 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

TSC22D1 encodes a leucine-zipper/TSC-box protein originally isolated as an immediate-early TGF-β1-inducible gene (PMID:15881652) that functions as a context-dependent regulator of cell proliferation, survival, and differentiation downstream of TGF-β signaling. Its expression is controlled largely post-transcriptionally: TGF-β1 stabilizes TSC22D1 mRNA by relieving 3'-UTR-mediated destabilization (PMID:12767908), and TGF-β acting through miR-216a-dependent loss of the stabilizing protein Ybx1 raises Tsc-22 protein levels (PMID:20713358), while the RNA-binding protein MEX3D directly binds and destabilizes TSC22D1 mRNA (PMID:35513372). The locus produces functionally opposing isoforms: a short cytoplasmic isoform that translocates to the nucleus upon apoptotic or DNA-damage stimuli to drive cell death, and a long isoform that supports proliferation and growth (PMID:19745830, PMID:21448135, PMID:34681573), a division mirrored in the Drosophila bunched locus where long isoforms promote growth and short isoforms antagonize them (PMID:18226226). Mechanistically, TSC22D1 amplifies TGF-β signaling by binding Smad3/Smad4 (PMID:15881652) and by competing with the Smad7/Smurf inhibitory complex at the type I receptor TβRI to block its ubiquitination and degradation, thereby sustaining Smad2/3 phosphorylation and myofibroblast differentiation (PMID:21791611); it also partners with Tfe3 at Col1a2 E-box enhancers to drive collagen expression (PMID:20713358). Its short isoform promotes apoptosis and cell-cycle exit by stabilizing p53 through inhibition of HDM2/E6-mediated poly-ubiquitination, activating p21 and PUMA (PMID:22870275), by repressing the anti-apoptotic targets Gadd45b (PMID:17533171) and GILZ (PMID:26752201), and acts as an effector of C/EBPβ in oncogene-induced senescence (PMID:21448135). Loss-of-function studies establish it as a negative growth regulator in salivary gland cancer (PMID:9458104, PMID:9459148) and a restraint on hematopoietic precursor expansion (PMID:19329776). Additional roles include modulation of WNK4 kinase signaling and renal Na⁺ handling via the long isoform localizing to WNK bodies [PMID:bio_10.1101_2024.12.12.628222] and reciprocal regulation of FoxO1 in pancreatic beta-cell function (PMID:40679946).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 Medium

    Established the molecular identity of TSC22D1 as a TGF-β-responsive leucine-zipper/TSC-box protein, defining the structural elements later dissected for function.

    Evidence Differential cDNA screening of TGF-β1-induced osteoblasts and protein characterization

    PMID:15881652

    Open questions at the time
    • Original isolation described only in secondary citations within the corpus
    • No structural model of the TSC-box or leucine zipper
  2. 1998 Medium

    Demonstrated that TSC22D1 acts as a tumor-suppressive negative growth regulator, answering whether its TGF-β inducibility translated into a growth-restraining cellular role.

    Evidence Sense/antisense transfection, nude-mouse tumorigenicity, antisense oligonucleotide and cycloheximide block in salivary gland cancer cells

    PMID:9458104 PMID:9459148

    Open questions at the time
    • Molecular mechanism of growth suppression not resolved
    • Isoform contributions not distinguished
  3. 2002 Medium

    Linked TSC22D1 subcellular trafficking to apoptotic signaling and mapped the active domains, showing cytoplasmic-to-nuclear translocation drives the cell-death response and the leucine zipper mediates growth suppression.

    Evidence GFP-fusion live-cell imaging, NLS/NES constructs, GAL4-reporter and soft-agar assays in cancer cells

    PMID:10879745 PMID:11095965 PMID:11836610 PMID:11944908

    Open questions at the time
    • Translocation trigger and transport machinery unidentified
    • Direct transcriptional targets of the leucine zipper not defined
  4. 2003 Medium

    Resolved how TGF-β raises TSC22D1 levels, showing regulation is post-transcriptional via 3'-UTR mRNA stabilization rather than promoter activation.

    Evidence Promoter-luciferase, RNA-protein binding, and heterologous mRNA stability reporter assays

    PMID:12767908

    Open questions at the time
    • Identity of the 40 kDa 3'-UTR-binding protein not established
    • Did not connect stabilization to downstream phenotype
  5. 2007 Medium

    Placed TSC22D1 upstream of specific apoptotic effectors as a transcriptional suppressor of Gadd45b, extending its role beyond TGF-β amplification.

    Evidence siRNA knockdown and oxazepam treatment with RT-PCR/western in mouse liver cells

    PMID:17533171

    Open questions at the time
    • Direct vs. indirect repression of Gadd45b not distinguished
    • No promoter occupancy data
  6. 2008 Medium

    Defined the opposing-isoform paradigm and a leucine-zipper-independent anti-apoptotic activity, reframing TSC22D1 as a locus encoding antagonistic long and short products.

    Evidence Drosophila bunched genetics, isoform-specific overexpression, yeast Bax-suppression assay and deletion mapping; fortilin yeast two-hybrid and Co-IP

    PMID:18226226 PMID:18325344 PMID:18355271 PMID:18375761

    Open questions at the time
    • Mammalian validation of fly isoform model incomplete at this stage
    • Mechanism by which the TSC22-domain peptide suppresses apoptosis unknown
  7. 2009 High

    Confirmed in mammalian cells that the short isoform induces death while the long isoform suppresses TGF-β-induced death, and linked TSC22D1 to restraint of hematopoietic precursor expansion via epigenetic silencing.

    Evidence Isoform-specific gain/loss in mammary epithelium and in vivo involution analysis; promoter methylation analysis and TSC-22 knockout mouse HPC repopulation assay

    PMID:19329776 PMID:19745830

    Open questions at the time
    • Molecular basis of opposing isoform outputs not fully defined
    • Tissue-specific isoform ratios uncharacterized
  8. 2010 High

    Identified a complete post-transcriptional control circuit (miR-216a/Ybx1) and a chromatin-level effector function with Tfe3, linking TGF-β input to collagen gene output.

    Evidence miRNA mimic/inhibitor, Ybx1 shRNA, RNP-IP, co-IP and ChIP on Col1a2 E-boxes in mesangial cells; siRNA in vascular SMCs for CNP

    PMID:20713358 PMID:20802130

    Open questions at the time
    • Whether Tfe3 partnership generalizes beyond Col1a2 unknown
    • Isoform identity at chromatin not specified
  9. 2011 High

    Established the core mechanism of TGF-β amplification—TSC22D1 displaces Smad7/Smurf from TβRI to block receptor degradation—and defined its role as a C/EBPβ effector in oncogene-induced senescence.

    Evidence Reciprocal Co-IP, ubiquitination assays, Smad7 siRNA epistasis and isoproterenol rat model; isoform-specific depletion/overexpression, proteasome inhibition and C/EBPβ epistasis in OIS

    PMID:21448135 PMID:21791611 PMID:21881999

    Open questions at the time
    • Stoichiometry of TβRI/Smad7 competition not resolved
    • How short-isoform induction is selectively triggered in senescence unclear
  10. 2012 Medium

    Identified a direct p53-stabilizing mechanism, explaining how the short isoform engages the apoptotic/cell-cycle-arrest program independently of transcription.

    Evidence Co-IP, ubiquitination assays, siRNA and overexpression with xenograft in cervical cancer cells

    PMID:22870275

    Open questions at the time
    • How TSC-22 blocks ubiquitination without affecting p53–HDM2 binding is unexplained
    • Structural basis of the aa100–200 interaction unknown
  11. 2016 Medium

    Extended the pro-apoptotic mechanism to immune cells, showing transcriptional repression of GILZ drives BIM-dependent caspase activation upon IL-2 deprivation.

    Evidence Overexpression in CTLL-2/NKL cells with IL-2 withdrawal, GILZ/BIM and caspase readouts

    PMID:26752201

    Open questions at the time
    • Direct vs. indirect GILZ repression not established
    • Isoform responsible not specified
  12. 2017 Medium

    Broadened the interactome to receptor tyrosine kinase signaling, showing TSC22D1 binds the CSF-1R kinase insert and suppresses AKT/ERK/NF-κB output.

    Evidence Co-IP, domain mapping, downstream signaling assays and xenograft

    PMID:29228668

    Open questions at the time
    • Whether interaction directly inhibits kinase activity unknown
    • Isoform specificity not determined
  13. 2021 Medium

    Resolved isoform-specific subcellular distributions and identified new nuclear binding partners, refining the spatial logic of TSC22D1 isoform function.

    Evidence GFP localization, subcellular fractionation, pull-down and MS in transfected cells

    PMID:34681573

    Open questions at the time
    • Functional consequences of Histone H1 and GNL3 binding not tested
    • Mitochondrial role of the short isoform undefined
  14. 2022 Medium

    Added MEX3D as a direct destabilizing regulator of TSC22D1 mRNA and BRD7 as a cooperating ERK-pathway partner, expanding upstream and signaling control.

    Evidence RNA pull-down, RIP and stability assays with MEX3D knockdown; Co-IP and ERK assays for BRD7

    PMID:35513372 PMID:36285148

    Open questions at the time
    • BRD7 interaction supported by a single Co-IP with limited detail
    • Interplay between MEX3D and TGF-β-driven stabilization untested
  15. 2025 Medium

    Defined organ-specific physiological roles, implicating TSC22D1 in renal WNK signaling, pancreatic beta-cell identity/insulin secretion via FoxO1, and NAFLD-associated endothelial dysfunction via TWEAK/FN14.

    Evidence WNK body localization and HEK293 WNK4 activity assays with NRBP1 KO mouse (preprint); siRNA depletion, RNA-Seq and Co-IP in INS-1E cells; single-cell transcriptomics, overexpression and AAV8-shRNA in NAFLD mice

    PMID:40679946 PMID:40901684 PMID:bio_10.1101_2024.12.12.628222

    Open questions at the time
    • Whether WNK-pathway role connects to the canonical TGF-β/apoptosis functions unknown
    • FoxO1 and TWEAK/FN14 mechanisms not integrated with isoform biology

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TSC22D1 assembles into a higher-order complex with NRBP1/WNK/SPAK via RΦ-motif/CCT interactions, and how this structural context governs the choice between its proliferative and pro-apoptotic outputs, remains unresolved.
  • Predicted multi-subunit complex computationally modeled but not experimentally reconstituted
  • No structure of any TSC22D1 protein complex
  • Determinants selecting long vs. short isoform function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 4 GO:0005739 mitochondrion 1
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
FOXO1NRBP1SMAD3SMAD4SMAD7TFE3TGFBR1TP53
Complex memberships
WNK bodies

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 TSC-22 (TSC22D1) was originally isolated as an immediate-early TGF-β1-inducible gene in mouse osteoblastic cells, encoding an ~18 kDa protein containing a leucine zipper motif and a TSC-box. Differential screening of osteoblast cDNA library; protein characterization Molecular and cellular biochemistry Medium 15881652
1998 Down-regulation of TSC-22 in human salivary gland cancer cells markedly enhanced their in vitro and in vivo growth, while up-regulation did not affect growth, establishing TSC-22 as a negative growth regulator relevant to salivary gland tumorigenesis. Sense/antisense cDNA transfection, ELISA protein quantification, in vitro growth assay, nude mouse tumorigenicity assay Cancer research Medium 9458104
1998 TSC-22 induction by vesnarinone required ongoing protein synthesis (blocked by cycloheximide), and antisense suppression of TSC-22 stimulated TYS cell growth and blocked vesnarinone's antiproliferative effect, confirming TSC-22 as a negative growth regulator. Antisense oligonucleotide treatment, cycloheximide block, cell growth assay British journal of cancer Medium 9459148
2000 TSC-22-GFP fusion protein localizes to the cytoplasm in living cells, but translocates to the nucleus in apoptotic cells; overexpression of cytoplasmic TSC-22 enhanced sensitivity to anticancer drugs (5-FU, CDDP, peplomycin) and markedly enhanced 5-FU-induced apoptosis. GFP fusion protein live-cell imaging, drug sensitivity assays, apoptosis assays in transfected cells Laboratory investigation Medium 10879745
2000 TSC-22-GFP translocates from cytoplasm to nucleus specifically during apoptosis; TSC-22 fused to GAL4-DNA binding domain showed transcriptional activation in CHO cells but not HeLa or yeast, and the leucine zipper domain had greater transcriptional activity than full-length TSC-22. GFP fusion protein live/apoptotic cell imaging, GAL4-reporter assays in multiple cell lines and yeast Biochemical and biophysical research communications Medium 11095965
2002 Cytoplasmic localization of TSC-22 (full-length, containing nuclear export signal) enhanced radiation sensitivity of salivary gland cancer cells, whereas the nuclear-only TSC-22 (NLS-TSC-22LZ) had marginal effect; cytoplasmic TSC-22 translocated to nucleus during radiation-induced apoptosis, demonstrating that cytoplasmic-to-nuclear translocation is important for the cell death signal. Transfection of TSC-22 constructs with/without NLS/NES, radiation sensitivity assays, subcellular localization imaging Biochemical and biophysical research communications Medium 11944908
2002 The leucine zipper domain of TSC-22 is the active domain for inhibiting anchorage-independent colony formation; full-length TSC-22 (cytoplasmic) had weaker effect, and nuclear leucine zipper construct was most potent. Transfection of domain-deletion constructs, anchorage-independent growth (soft agar) assay Oncology reports Medium 11836610
2002 TSC-22 is a downstream effector of both PPARγ and TGF-β signaling in intestinal epithelial cells; transfection of wild-type TSC-22 reduced growth and increased p21, and a dominant-negative TSC-22 (both repressor domains deleted) reversed p21 induction and growth inhibition by PPARγ or TGF-β activation. PPARγ ligand treatment, TGF-β treatment, wild-type and dominant-negative TSC-22 transfection, p21 immunoblot, growth assay The Journal of biological chemistry Medium 12468551
2003 TGF-β1 upregulates TSC-22 mRNA through mRNA stabilization rather than transcriptional activation: the TSC-22 promoter was not activated by TGF-β signaling, but the 3'-UTR (containing Shaw-Kamens AUUUA sequences) destabilized heterologous mRNA, and TGF-β1 relieved this destabilization; a 40 kDa protein bound the 3'-UTR and this complex was decreased by TGF-β1. Promoter-luciferase assay, RNA-protein binding assay, heterologous mRNA stability reporter assay Biochemical and biophysical research communications Medium 12767908
2005 Tsc-22 binds directly to Smad3 and Smad4 and modulates their transcriptional activity, enhancing TGF-β-dependent signaling; Tsc-22 also induced erythroid cell differentiation. Co-immunoprecipitation, transcriptional reporter assays, differentiation assays Molecular and cellular biochemistry Medium 15881652
2007 TSC-22 is a transcriptional suppressor of Gadd45b in mouse liver cells: siRNA knockdown of Tsc-22 increased Gadd45b gene and protein expression over time, and oxazepam treatment also decreased Tsc-22 and increased Gadd45b, placing Tsc-22 upstream of Gadd45b in an antiapoptotic pathway. siRNA knockdown, RT-PCR, western blot, oxazepam chemical treatment Toxicological sciences Medium 17533171
2008 TSC-22 interacts with fortilin (a nuclear anti-apoptotic protein), and fortilin overexpression reverses TSC-22-mediated apoptosis by promoting TSC-22 protein degradation; fortilin siRNA knockdown increased apoptosis. Yeast two-hybrid screening, Co-IP, overexpression/siRNA in ovarian carcinoma cells, apoptosis assay FEBS letters Medium 18325344
2008 The Drosophila TSC-22 homolog Bunched (Bun) large isoforms promote cellular growth and proliferation; loss of large isoforms increases apoptosis and reduces cell size and division frequency in S2 cells and follicle cells, demonstrating a growth-promoting (not suppressive) function for the long isoform. Drosophila genetics (loss-of-function clonal analysis), S2 cell RNAi depletion, cell size and division measurements Proceedings of the National Academy of Sciences Medium 18375761
2008 The Drosophila bunched large isoform BunA promotes growth (cell number and cell size), while short isoforms BunB and BunC antagonize BunA function, establishing opposing roles for long vs. short isoforms at the single TSC-22/bun locus. Unbiased genetic screen, bun loss-of-function mutants, isoform-specific overexpression, cell size and number quantification BMC developmental biology Medium 18226226
2008 A 16-residue sequence within the conserved 56-residue TSC22 domain (not the leucine zipper) is necessary for TSC-22's anti-apoptotic activity in yeast Bax-suppression assays; deletion mutagenesis and two-hybrid screening showed the antiapoptotic effect is independent of leucine zipper-mediated transcription. Yeast Bax-suppression assay, deletion mutagenesis, genome-wide two-hybrid screen, yeast overexpression/knockout FEMS yeast research Medium 18355271
2009 TSC-22D1 isoform 2 (short isoform) induces cell death in mammary epithelial cells and is upregulated during mammary gland involution, while isoform 1 (long isoform) suppresses TGF-β-induced cell death and enhances proliferation; the two isoforms exert opposing effects on cell survival. Isoform-specific overexpression/depletion in mammary epithelial cell lines, mammary gland in vivo expression analysis, cell death assays Cell death and differentiation Medium 19745830
2009 TSC-22 promoter is hypermethylated in T/NK LGL leukemia, silencing its expression; targeted disruption of TSC-22 in mice enhanced proliferation and in vivo repopulation of hematopoietic precursor cells (HPCs), demonstrating a role for TSC-22 in restraining HPC expansion. Methylation analysis, 5-aza-2'-deoxycytidine treatment in vivo, TSC-22 knockout mouse model, HPC repopulation assay Blood High 19329776
2010 TGF-β increases Tsc-22 protein levels post-transcriptionally in mesangial cells via miR-216a-mediated down-regulation of Ybx1; Ybx1 forms a ribonucleoprotein complex with Tsc-22 mRNA that stabilizes it, and TGF-β disrupts this complex to increase Tsc-22 protein. Tsc-22 then interacts with Tfe3 and both occupy E-box enhancers of Col1a2 to drive collagen expression. miRNA mimic/inhibitor oligonucleotides, Ybx1 shRNA knockdown, RNP complex co-immunoprecipitation, ChIP assay for Tsc-22 and Tfe3 on Col1a2 E-boxes, co-IP for Tsc-22/Tfe3 interaction The Journal of biological chemistry High 20713358
2010 TSC22D1 is required for TGF-β1- and PDGF-BB-stimulated CNP (C-type natriuretic peptide) expression in human vascular smooth muscle cells; siRNA suppression of TSC22D1 (~90% knockdown) reduced TGF-β- and PDGF-stimulated CNP expression by 45–65%, establishing TSC22D1 as an enhancer of CNP transcription downstream of TGF-β. siRNA knockdown of TSC22D1, qRT-PCR for CNP and TSC22D1 mRNA, TGF-β1/PDGF-BB treatment in primary human vascular SMCs American journal of physiology. Heart and circulatory physiology Medium 20802130
2011 TSC-22 facilitates TGF-β signaling by interacting with TβRI and Smad7 in mutually exclusive ways, disrupting the Smad7/Smurf-TβRI association and thereby preventing TβRI ubiquitination and degradation. This leads to enhanced Smad2/3 phosphorylation and promotes cardiac myofibroblast differentiation. The stimulatory effect of TSC-22 is abolished when Smad7 is silenced. Co-IP of TSC-22 with TβRI and Smad7, ubiquitination assays, Smad2/3 phosphorylation immunoblot, Smad7 siRNA epistasis, myofibroblast differentiation markers (α-SMA, PAI-1, fibronectin, collagen I), isoproterenol rat model Molecular and cellular biology High 21791611
2011 BRAF(E600)-induced senescence upregulates only the short TSC22D1 transcript (>100-fold); the long TSC22D1 protein variant is degraded by proteasomal degradation. Short and long TSC22D1 variants form complexes with their dimerization partner THG1 and exert opposing functions: depletion of the short form or overexpression of the long form abrogates oncogene-induced senescence (OIS). TSC22D1 acts as a critical effector of C/EBPβ in OIS, controlling inflammatory factors and p15(INK4B). Gene expression profiling, isoform-specific depletion (short form), long isoform overexpression, proteasome inhibition, senescence assays, C/EBPβ epistasis analysis The EMBO journal High 21448135
2011 PKC regulation of TGF-β signaling depends on Tsc-22 inducibility: in cells where Tsc-22 is induced, Tsc-22 enhances TGF-β-dependent signaling, and a dominant-negative Tsc-22 mutant blocks this enhancement, demonstrating cell-type-specific modulation of the Smad-PKC axis by Tsc-22. Dominant-negative TSC-22 mutant transfection, TGF-β signaling reporter assays, comparison across cell types Molecular and cellular biochemistry Low 21881999
2012 TSC-22 binds directly to p53 at the motif between amino acids 100–200, inhibiting HDM2- and E6-mediated poly-ubiquitination and degradation of p53, thereby stabilizing p53 and activating p21(Waf1/Cip1) and PUMA expression. TSC-22 siRNA knockdown enhanced p53 poly-ubiquitination. Notably, TSC-22 did not affect the p53–HDM2 interaction itself. Co-IP of TSC-22 and p53, ubiquitination assays, siRNA knockdown, overexpression in cervical cancer cells and xenograft model, p21/PUMA western blot PloS one Medium 22870275
2016 TSC-22 promotes apoptosis in IL-2-deprived T-lymphocytes by inhibiting GILZ expression at the transcriptional level, resulting in increased BIM expression and elevated caspase-9 and caspase-3 activities. TSC-22 overexpression in CTLL-2 and NKL cell lines, IL-2 withdrawal apoptosis assay, GILZ mRNA quantification, BIM/caspase activity measurements Journal of cellular biochemistry Medium 26752201
2017 TSC-22 interacts with the intracellular tyrosine kinase insert domain (aa 539–749) of CSF-1R, blocking AKT and ERK signaling and suppressing NF-κB transcriptional activity; TSC-22 overexpression also decreased CSF-1R protein levels, disrupting its autocrine signaling loop. Co-IP of TSC-22 and CSF-1R, domain mapping, AKT/ERK/NF-κB signaling assays, CSF-1R protein level quantification, xenograft tumor model Oncotarget Medium 29228668
2019 TSC22D4-TSC22D1 short isoform heterodimers promote cell cycle exit and escape from proliferation in medulloblastoma cells, whereas the TSC22D1 long isoform supports cell proliferation independently of TSC22D4; silencing specific isoforms affects cell-cycle progression. siRNA isoform-specific knockdown of TSC22D1 long/short and TSC22D4, cell cycle analysis in DAOY medulloblastoma cells Journal of cellular physiology Medium 30912127
2021 TSC22D1-1 (long isoform) localizes predominantly to the nucleus; TSC-22 (TSC22D1-2, short isoform) localizes to the cytoplasm (mainly mitochondria) and translocates to nucleus after DNA damage; TSC22(86) (TSC22D1-3) localizes to both compartments. Pull-down and in vivo binding assays identified Histone H1 as a binding partner of TSC22D1-2 and TSC22D1-3 in the nucleus, and GNL3/nucleostemin as a binding partner of TSC22D1-2 in the nucleus. GFP-fusion localization imaging, subcellular fractionation, in vitro pull-down assays, in vivo binding assays, mass spectrometry International journal of molecular sciences Medium 34681573
2022 MEX3D RNA-binding protein directly binds TSC22D1 mRNA and destabilizes it, reducing TSC22D1 expression in cervical cancer; MEX3D knockdown increased TSC22D1 levels, and this was confirmed by RNA pull-down, RNA immunoprecipitation, and mRNA stability assays. RNA pull-down, RNA immunoprecipitation (RIP), mRNA stability assays, MEX3D knockdown, western blot Cell death discovery Medium 35513372
2022 TSC-22 directly interacts with BRD7 and potentiates BRD7-mediated inactivation of the ERK signaling pathway in ovarian cancer cells. Co-IP identification of TSC-22/BRD7 interaction, ERK pathway activity assays with TSC-22 overexpression Development & Reproduction Low 36285148
2024 TSC22D1 long isoform (TSC22D1.1) localizes to WNK bodies (cytoplasmic biomolecular condensates) in the distal convoluted tubule of the kidney and positively modulates WNK4 signaling; long TSC22D isoforms and NRBP1 increase WNK4 activity in HEK293 cells, and this is associated with regulation of NCC phosphorylation and Na+ reabsorption. Subcellular localization in kidney DCT cells, HEK293 WNK4 activity assay, DCT-specific NRBP1 knockout mouse model, NCC phosphorylation immunoblot bioRxivpreprint Medium bio_10.1101_2024.12.12.628222
2024 TSC22D1 contains an RΦ-motif that interacts with the CCT-like domain of the pseudokinase NRBP1, and AlphaFold-3 modeling predicts TSC22D1 forms part of a multi-subunit complex with WNK1, SPAK, and TSC22D4 via RΦ-motif interactions with CCT domains. Motif interaction analysis, immunoprecipitation, mass spectrometry, AlphaFold-3 structural modeling bioRxivpreprint Low bio_10.1101_2024.06.26.600905
2025 TSC22D1 interacts with FoxO1 in a reciprocal manner to regulate pancreatic beta cell function; TSC22D1 depletion in INS-1E cells enhanced expression of beta cell identity genes (Ins1, Ins2, Pdx1, Slc2a2, Nkx6.1) and promoted glucose-stimulated insulin secretion without altering intracellular insulin content. TSC22D1 siRNA depletion in INS-1E cells, glucose-stimulated insulin secretion assay, gene expression profiling (RNA-Seq), interactome analysis, Co-IP of TSC22D1 and FoxO1 The FEBS journal Medium 40679946
2025 TSC22D1 drives liver sinusoidal endothelial cell (LSEC) dysfunction and M1 macrophage polarization via the TWEAK/FN14 signaling pathway; TSC22D1 overexpression in LSECs increased pro-inflammatory cytokine secretion and LSEC microvascularization/EndMT, and TWEAK inhibition attenuated these effects; AAV8-shRNA inhibition of TSC22D1 in vivo reduced NAFLD progression. Single-cell transcriptomic analysis, TSC22D1 overexpression in human LSECs, flow cytometry, ELISA, TWEAK inhibitor treatment, AAV8-shRNA in vivo knockdown in NAFLD mice World journal of gastroenterology Medium 40901684

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 45 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
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 31 17174532
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
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
2025 TSC22D1 promotes liver sinusoidal endothelial cell dysfunction and induces macrophage M1 polarization in non-alcoholic fatty liver disease. World journal of gastroenterology 2 40901684
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
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

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