Affinage

TSPYL2

Testis-specific Y-encoded-like protein 2 · UniProt Q9H2G4

Length
693 aa
Mass
79.4 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 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

TSPYL2 (also CDA1/DENTT/TSPX) is a nucleus- and nucleolus-localized chromatin-associated regulator that couples cell-cycle control, the DNA-damage response, and TGF-β signaling to act as a multi-context growth suppressor (PMID:11395479, PMID:17317670, PMID:21738728). It is a phosphosubstrate of cyclin-CDK complexes (cyclin D1/CDK4, cyclin A/CDK2, cyclin B/CDK1), and CDK-site phosphorylation is required for its growth-arresting activity (PMID:11395479). After DNA damage TSPYL2 enforces the G1 checkpoint by enabling p53-dependent transcription of p21: it stabilizes p53 through MDM2 inactivation and drives p21 induction via p53- and MEK/ERK-dependent routes, and it acts downstream of p53 since knockout cells accumulate p53 normally yet fail to induce p21 (PMID:17317670, PMID:21738728). A recurrent biochemical theme is its antagonism of the deacetylase SIRT1 — by disrupting SIRT1's engagement of substrates, TSPYL2 promotes p300-mediated p53 acetylation and apoptosis, and preserves the acetylation of FOXO3 and AKT to constrain DNA-damage repair, AKT signaling, and therapy resistance in cancer cells (PMID:30050056, PMID:35192400, PMID:37696385). TSPYL2 also operates within transcriptional/chromatin complexes: it joins the REST/NRSF repressor to potentiate TGF-β-driven cell-cycle arrest and repress the TrkC oncogene, and it binds CBP and EZH2 to control H3K27me3 and the expression of synaptic and developmental genes (Grin2a, Grin2b, Bdnf, Egr3) underlying hippocampal LTP and memory (PMID:24413569, PMID:25613376, PMID:30051352). Through enhancement of TGF-β/Smad3 signaling it restrains fibroblast-to-myofibroblast transition and fibrosis and protects against diabetic vascular and renal injury (PMID:29311219, PMID:30425061, PMID:37391440). TSPYL2 protein levels are set by ubiquitin-proteasome turnover via the E3 ligase ZFP91 and the CRL2-APPBP2 complex, the latter linking its degradation to mesenchymal stem cell senescence through p21 (PMID:36090681, PMID:38170390).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 High

    Established TSPYL2/CDA1 as a CDK-phosphorylated nuclear/nucleolar protein whose overexpression arrests cell growth, defining it as a cell-cycle-coupled growth suppressor.

    Evidence In vitro kinase assays with recombinant cyclins/CDKs, cell fractionation, transgene overexpression with CDK-site mutagenesis and BrdU incorporation in HeLa cells

    PMID:11395479

    Open questions at the time
    • Functional consequence of each individual CDK phosphorylation event not resolved
    • Molecular mechanism by which growth arrest is executed not defined in this study
  2. 2001 Medium

    Independently identified the same protein (DENTT) as a TGF-β1-inducible gene whose nucleolar localization depends on a bipartite NLS and whose induction tracks with growth suppression, linking it to TGF-β biology.

    Evidence Differential mRNA display, Northern blot, EGFP-NLS deletion constructs in COS-7, soft agarose colony assay in NSCLC cells

    PMID:11318608

    Open questions at the time
    • Direct demonstration that DENTT acts within the TGF-β pathway not yet shown
    • Single-lab localization with overexpressed tagged constructs
  3. 2005 Medium

    Showed the protein specifically potentiates TGF-β transcriptional output rather than acting as a general transcription enhancer.

    Evidence Transient transfection with TGF-β-responsive (3TP-Lux, CAGA12-Lux) versus retinoic-acid-responsive luciferase reporters in lung cells

    PMID:15823505

    Open questions at the time
    • Mechanism of reporter potentiation (direct vs indirect) unresolved
    • No endogenous target genes identified
  4. 2007 High

    Defined the mechanism of growth arrest — TSPYL2 stabilizes p53 via MDM2 inactivation and induces p21 through p53- and MEK/ERK-dependent transcription, and is itself a DNA-damage-responsive gene.

    Evidence siRNA knockdown, p21 promoter reporter deletions, pharmacologic MEK inhibition, camptothecin damage model in cultured cells

    PMID:17317670

    Open questions at the time
    • Biochemical basis of MDM2 inactivation by TSPYL2 not defined
    • How TSPYL2 activates ERK signaling unknown
  5. 2008 Medium

    Demonstrated TSPYL2 is downregulated and epigenetically silenced in tumors and suppresses anchorage-independent growth and migration, establishing it as a candidate tumor suppressor.

    Evidence Stable overexpression, colony/soft-agar/migration assays, demethylating agent treatment, RT-PCR on primary tumors

    PMID:18381359

    Open questions at the time
    • Causal silencing mechanism (promoter methylation site) not mapped
    • Single-lab tumor sample analysis
  6. 2011 High

    Genetically separated TSPYL2 function from p53 stabilization, showing it acts downstream of p53 to enable p21 transcription and G1 checkpoint maintenance after DNA damage.

    Evidence Tspyl2 knockout mice, gamma irradiation of primary MEFs/thymocytes, cell-cycle analysis, p21 expression assays

    PMID:21738728

    Open questions at the time
    • Molecular step linking TSPYL2 to p21 promoter activation not defined
    • Reconciliation with the 2007 MDM2/p53-stabilization model unresolved
  7. 2014 High

    Revealed a neuronal transcriptional function — TSPYL2 binds CBP and directly regulates NMDA receptor subunit genes, with loss impairing hippocampal LTP and memory.

    Evidence Tspyl2 KO mice, Co-IP, ChIP and reporter assays at Grin2a/Grin2b, electrophysiology, fear conditioning

    PMID:24413569

    Open questions at the time
    • Whether TSPYL2 activates or recruits CBP enzymatic activity not resolved
    • Direct DNA-binding versus adaptor role at promoters unclear
  8. 2015 High

    Placed TSPYL2 inside the REST/NRSF repressor complex co-regulating TGF-β-induced arrest and repressing the TrkC oncogene, linking its TGF-β and tumor-suppressor activities.

    Evidence Co-IP of TSPYL2–REST, shRNA knockdown, mammary epithelial transformation assay, TGF-β arrest assay

    PMID:25613376

    Open questions at the time
    • Stoichiometry and architecture of the TSPYL2–REST complex unknown
    • How the complex intersects with Smad-dependent TGF-β transcription not defined
  9. 2018 High

    Identified SIRT1 inhibition as a core biochemical activity — TSPYL2 disrupts SIRT1 substrate engagement to promote p300-mediated p53 acetylation and DNA-damage apoptosis.

    Evidence siRNA knockdown, Co-IP of TSPYL2–SIRT1 and TSPYL2–p300, p53 acetylation and apoptosis assays with SIRT1/p300 epistasis

    PMID:30050056

    Open questions at the time
    • Direct enzymatic inhibition of SIRT1 versus competitive sequestration not distinguished
    • Structural basis of TSPYL2–SIRT1 contact unknown
  10. 2018 High

    Extended TSPYL2's chromatin role to PRC2, showing it interacts with EZH2 and co-occupies promoters to regulate H3K27me3 and developmental/synaptic gene expression.

    Evidence Tspyl2 KO mice, Co-IP of TSPYL2–EZH2, ChIP-seq in hippocampal neurons/neuroblastoma, GSK126 rescue, qRT-PCR

    PMID:30051352

    Open questions at the time
    • Whether TSPYL2 promotes or restrains EZH2 catalytic activity at target loci not resolved
    • Relationship between CBP-activating and EZH2-associated functions unclear
  11. 2018 High

    Established a protective in vivo role in diabetic vasculature via TGF-β-driven collagen and reduced inflammation, with human aneurysm tissue validation.

    Evidence CDA1, ApoE, and double-KO mice, diabetes and angiotensin II aneurysm models, TGF-β/collagen/macrophage readouts, human biopsy Western blot

    PMID:29311219

    Open questions at the time
    • Cell-type responsible for the protective effect not pinpointed
    • Mechanistic link from TSPYL2 to MMP12/macrophage suppression incomplete
  12. 2018 High

    Identified CDA1BP1 as a binding partner required for TSPYL2's pro-fibrotic activity and validated the interaction as a druggable target with a peptide inhibitor.

    Evidence Co-IP of CDA1–CDA1BP1, CDA1BP1 KO mice, competitive peptide assays, HK-2 cell collagen, diabetic kidney histology in vivo

    PMID:30425061

    Open questions at the time
    • Molecular identity/domain of the CDA1–CDA1BP1 interface beyond peptide mapping not fully defined
    • How CDA1BP1 binding modulates TGF-β output mechanistically unclear
  13. 2022 Medium

    Connected the SIRT1-antagonism mechanism to therapy resistance, showing TSPYL2 preserves FOXO3 acetylation to limit DNA-damage repair and gefitinib resistance in colorectal cancer.

    Evidence TSPYL2 knockdown/overexpression in CRC cells, SIRT1/FOXO3 acetylation Western blot, tumor xenografts

    PMID:35192400

    Open questions at the time
    • Limited biochemical detail on FOXO3 acetylation site regulation
    • Single-lab study
  14. 2023 Medium

    Defined ZFP91 as an E3 ligase that ubiquitinates and degrades TSPYL2, and linked its stabilization to gemcitabine sensitivity in pancreatic cancer.

    Evidence Co-IP of ZFP91–TSPYL2, ubiquitination assay, overexpression/knockdown, drug-resistance and xenograft assays, ginsenoside Rg3 modulation

    PMID:36090681

    Open questions at the time
    • Ubiquitination site(s) on TSPYL2 not mapped
    • Whether ZFP91 regulation is constitutive or signal-dependent unknown
  15. 2023 High

    Identified a second degradation route via CRL2-APPBP2 and tied TSPYL2 turnover to p21 control and mesenchymal stem cell senescence.

    Evidence CRISPR CUL2 KO in hESCs, Cullin knockdown screen, APPBP2 substrate-receptor identification, proteasome inhibition, senescence and p21 readouts

    PMID:38170390

    Open questions at the time
    • Degron recognized by APPBP2 not defined
    • Crosstalk between ZFP91 and CRL2-APPBP2 pathways unresolved
  16. 2023 High

    Demonstrated therapeutic anti-fibrotic action — AAV9-delivered TSPYL2 represses TGF-β/Smad3 signaling and blocks fibroblast-to-myofibroblast transition in lung fibrosis.

    Evidence Lentiviral OE/siRNA in HFL1 cells, AAV9-Tspyl2 intratracheal delivery in bleomycin model, Smad3 phosphorylation, histology, ECM gene expression

    PMID:37391440

    Open questions at the time
    • Apparent context-dependent dual effect on TGF-β (potentiation versus repression) across tissues not reconciled
    • Direct molecular target on the Smad3 axis not identified
  17. 2023 Medium

    Showed TSPYL2 suppresses AKT signaling in thyroid cancer by inhibiting SIRT1-mediated AKT deacetylation, reinforcing SIRT1 antagonism as a generalizable tumor-suppressive mechanism.

    Evidence Co-IP of TSPYL2–SIRT1, AKT acetylation/phosphorylation Western blot, KD/OE in thyroid cancer cells, xenografts

    PMID:37696385

    Open questions at the time
    • AKT acetylation site and its phosphorylation linkage not biochemically detailed
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TSPYL2 reconciles its opposing context-dependent effects on TGF-β signaling (potentiation in lung/vascular protection versus its role across tumor and fibrosis settings) and whether it binds DNA directly or acts purely as a chromatin/complex adaptor remain unresolved.
  • No structural model of TSPYL2 or its complexes
  • Direct DNA-binding versus adaptor function not established
  • Unifying biochemical activity reconciling p53, SIRT1, REST, CBP, and EZH2 functions not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005730 nucleolus 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-73894 DNA Repair 2 R-HSA-4839726 Chromatin organization 1 R-HSA-5357801 Programmed Cell Death 1
Partners
APPBP2CBPCDA1BP1EP300EZH2RESTSIRT1ZFP91
Complex memberships
REST/NRSF repressor complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CDA1 (TSPYL2) is phosphorylated in HeLa cells and by cyclin D1/CDK4, cyclin A/CDK2, and cyclin B/CDK1 in vitro. It localizes to the nucleus and nucleolus in HeLa cells. Overexpression arrests cell growth, colony formation, cell density, and BrdU uptake in a dose-dependent manner; this growth arrest is abolished by mutation of the two CDK consensus phosphorylation sites. In vitro kinase assays with recombinant cyclins/CDKs, cell fractionation, transfection with CDA1 transgene and N-terminal/C-terminal truncations, BrdU incorporation, CDK phosphorylation site mutagenesis The Journal of biological chemistry High 11395479
2007 CDA1 (TSPYL2) induces p53 protein accumulation (by inactivating the ubiquitin ligase MDM2, reducing p53 degradation) and transcriptionally up-regulates p21(Waf1/Cip1) via p53-dependent and MEK/ERK1/2 MAPK-dependent pathways. CDA1 activates ERK1/2 phosphorylation; MEK inhibitors PD98059 and U0126 block this and abrogate p21 induction. DNA damage (camptothecin) increases CDA1 mRNA/protein and induces p53; CDA1 knockdown markedly attenuates damage-induced p53 induction. siRNA knockdown, p53 siRNA, luciferase reporter assays with p21 promoter deletions, Western blot for p53/MDM2/ERK/p21, qRT-PCR, pharmacologic MEK inhibition, camptothecin DNA damage model The Journal of biological chemistry High 17317670
2001 DENTT (TSPYL2) mRNA is induced ~3-fold by TGF-β1 in TGF-β1-responsive NSCLC cells (NCI-H727) but not in non-responsive NSCLC cells. EGFP-tagged DENTT localizes to the nucleolus and cytoplasm; deletion of the bipartite NLS-1 excludes DENTT from the nucleolus. TGF-β1 induction of DENTT correlates with extracellular matrix gene induction and inhibition of colony formation in soft agarose. Differential mRNA display, Northern analysis, EGFP-tagged localization constructs with NLS deletions in COS-7 cells, soft agarose colony assay Genomics Medium 11318608
2005 DENTT (TSPYL2) ectopic expression significantly increases TGF-β1-responsive 3TP-Lux and CAGA12-Lux reporter transcription in lung cells when TGF-β1 is added, but has no significant effect on retinoic acid-responsive element reporter transcription, indicating DENTT specifically potentiates TGF-β signaling at the transcriptional level. Transient transfection of DENTT expression plasmid with TGF-β1-responsive luciferase reporters (3TP-Lux, CAGA12-Lux) in 12MBr6 and NCI-H727 cells; TGF-β1 and retinoic acid treatments Biochimica et biophysica acta Medium 15823505
2008 DENTT (TSPYL2) overexpression in lung (A549) and breast (MCF-7) cancer cells reduces anchorage-dependent and anchorage-independent growth and inhibits cell migration. DENTT mRNA and protein are markedly downregulated in primary human and mouse tumors and tumor cell lines. Demethylating agents increase DENTT expression, suggesting epigenetic silencing. DENTT expression parallels TGF-β1 and ectopic TGF-β1 increases DENTT mRNA/protein. Stable overexpression, colony formation assay, soft agar assay, cell migration assay, Western blot, demethylating agent treatment, RT-PCR in primary tumor samples Carcinogenesis Medium 18381359
2011 TSPYL2 is required for G1 checkpoint maintenance after DNA damage. Tspyl2 knockout mouse embryonic fibroblasts are impaired in G1 arrest following gamma irradiation despite proper p53 protein accumulation, due to defective transcriptional activation of p21, indicating TSPYL2 acts downstream of p53 to enable p21 induction. Tspyl2 knockout mouse generation (targeted disruption), gamma irradiation of primary MEFs and thymocytes, cell cycle analysis, p21 RT-PCR/protein assay PloS one High 21738728
2014 TSPYL2 interacts with CREB-binding protein (CBP) and regulates expression of NMDA receptor subunits GluN2A (Grin2a) and GluN2B (Grin2b) in the hippocampus. Tspyl2 knockout mice show reduced GluN2A and GluN2B protein; luciferase reporter assays and chromatin immunoprecipitation support direct transcriptional regulation of Grin2a and Grin2b by TSPYL2. Loss of TSPYL2 impairs hippocampal LTP and fear learning/memory. Tspyl2 knockout mice, Co-immunoprecipitation (TSPYL2–CBP interaction), ChIP at Grin2a/Grin2b promoters, luciferase reporter assays, electrophysiology (LTP), fear conditioning Scientific reports High 24413569
2015 TSPYL2 is a component of the REST/NRSF transcriptional repressor complex. TSPYL2 and REST co-regulate TGF-β signaling: knockdown of either causes transformation of human mammary epithelial cells. The TSPYL2/REST complex represses expression of TrkC (proto-oncogene NTRK3), and cell-cycle arrest induced by TGF-β requires both REST and TSPYL2. Co-immunoprecipitation (TSPYL2–REST interaction), shRNA knockdown of TSPYL2 and REST, mammary epithelial cell transformation assay, TGF-β cell-cycle arrest assay, TrkC expression analysis Cell death and differentiation High 25613376
2018 TSPYL2 inhibits SIRT1 (disrupting SIRT1's association with target proteins) and promotes p300 acetylation and activation upon DNA damage, thereby stimulating p53 acetylation and p53-dependent apoptosis. Cells silenced for TSPYL2 are defective in p53 activation and apoptosis induction after DNA damage, in a SIRT1- and p300-dependent manner. siRNA knockdown of TSPYL2, Co-immunoprecipitation (TSPYL2–SIRT1, TSPYL2–p300 interactions), p53 acetylation assays, apoptosis assays, epistasis by rescue with SIRT1/p300 manipulation Cell death and differentiation High 30050056
2018 TSPYL2 regulates expression of EZH2 target genes in neurons. Tspyl2 knockout mice have elevated H3K27me3 in the hippocampus; TSPYL2 interacts with EZH2 by Co-IP and co-occupies target gene promoters (ChIP). Loss of TSPYL2 reduces expression of developmental/synaptic genes including Bdnf, Egr3, Grin2c, Igf1, Gbx2, and Acvrl1. EZH2 inhibitor GSK126 rescues reduced expression in mutant neurons. Tspyl2 KO mice, Co-immunoprecipitation (TSPYL2–EZH2), ChIP-sequencing and ChIP in hippocampal neurons/neuroblastoma cells, pharmacologic EZH2 inhibition (GSK126), qRT-PCR Molecular neurobiology High 30051352
2018 In diabetic mice, CDA1 (TSPYL2) expression is upregulated in the aorta and confers protection against aortic aneurysm through enhanced TGF-β signaling, increased collagen expression, and reduced macrophage infiltration. CDA1/ApoE double-knockout diabetic mice develop aortic aneurysms not seen in ApoE-KO diabetic mice; CDA1 deletion in the angiotensin II model also abrogates diabetes-mediated protection. CDA1 aortic expression is downregulated ~70% in human abdominal aortic aneurysm biopsies. CDA1 KO, ApoE KO, CDA1/ApoE double-KO mouse models; diabetes induction; angiotensin II aneurysm model; TGF-β signaling and collagen immunostaining/Western blot; macrophage and MMP12 analysis; human biopsy Western blot Diabetes High 29311219
2018 A novel CDA1-binding protein (CDA1BP1) was identified as a regulator of CDA1 (TSPYL2) profibrotic activity. CDA1BP1 binds CDA1; genetic deletion of CDA1BP1 attenuates renal fibrosis in diabetic mice. Synthetic CDA1BP1 peptides competitively inhibit CDA1–CDA1BP1 binding in vitro and reduce collagen expression in HK-2 cells. A retro-inverso d-amino acid peptide (CHA-061) targeting this interaction attenuates renal extracellular matrix accumulation and glomerular injury in vivo. Co-immunoprecipitation (CDA1–CDA1BP1), CDA1BP1 KO mouse, competitive peptide inhibition assays in vitro, HK-2 cell collagen expression, in vivo diabetic mouse kidney histology and gene expression Diabetes High 30425061
2022 TSPYL2 inhibits SIRT1-mediated deacetylation of FOXO3, thereby reducing gefitinib resistance and DNA damage repair in colorectal cancer cells. TSPYL2 knockdown promotes gefitinib resistance; TSPYL2 overexpression inhibits DNA damage repair. Mechanistically, TSPYL2 suppresses SIRT1, which reduces SIRT1-mediated FOXO3 deacetylation, and TSPYL2 inhibits tumor growth and resistance in vivo. TSPYL2 knockdown/overexpression in CRC cells, immunofluorescence, Western blot for SIRT1/FOXO3 acetylation/phosphorylation, tumor xenograft experiments Future medicinal chemistry Medium 35192400
2023 ZFP91 interacts with TSPYL2, induces its poly-ubiquitination, and promotes its proteasomal degradation. Ginsenoside Rg3 weakens ZFP91-induced TSPYL2 poly-ubiquitination and degradation. Enforced TSPYL2 expression increases gemcitabine sensitivity in pancreatic adenocarcinoma cells. Co-immunoprecipitation (ZFP91–TSPYL2), ubiquitination assay, TSPYL2 overexpression/knockdown, cell viability/drug resistance assays, in vivo tumor xenograft Journal of ginseng research Medium 36090681
2023 CRL2APPBP2 (CUL2–APPBP2 E3 ligase complex) targets TSPYL2 for ubiquitin–proteasome-mediated degradation via the substrate receptor APPBP2. CUL2 deletion accelerates hMSC senescence; TSPYL2 accumulates upon CUL2 loss and down-regulates P21(waf1/cip1), thereby counteracting senescence. This places TSPYL2 degradation as a mechanism to delay mesenchymal stem cell aging. CRISPR/Cas9 CUL2 KO in hESCs, hMSC differentiation, individual Cullin knockdown screen, APPBP2 substrate receptor identification, proteasome inhibition, senescence assays, p21 Western blot Science China. Life sciences High 38170390
2023 TSPYL2 (CDA1) overexpression via AAV9 gene delivery inhibits bleomycin-induced pulmonary fibrosis in mice by repressing TGF-β/Smad3 signaling and inhibiting lung fibroblast-to-myofibroblast transition. In vitro, CDA1 overexpression in HFL1 fibroblasts reduces TGF-β1-induced pro-fibrotic cytokines, ECM protein expression, and cell proliferation/migration; CDA1 knockdown enhances these effects. Lentiviral overexpression, siRNA knockdown in HFL1 cells, AAV9-Tspyl2 intratracheal delivery in BLM mouse model, Smad3 phosphorylation assay, histology, ECM gene expression Cell death & disease High 37391440
2023 TSPYL2 interacts with SIRT1 (Co-IP) in thyroid cancer cells and inhibits AKT activation by upregulating AKT acetylation level, reducing SIRT1-mediated AKT deacetylation. Knockdown of TSPYL2 increases SIRT1–AKT association and AKT phosphorylation; TSPYL2 overexpression reverses these effects and suppresses thyroid cancer cell proliferation, migration, invasion, and in vivo tumor growth. Co-immunoprecipitation (TSPYL2–SIRT1), AKT acetylation/phosphorylation Western blot, TSPYL2 KD/OE in TPC-1 and IHH-4 cells, tumor xenograft Experimental cell research Medium 37696385

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 887 16960145
2012 Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Science translational medicine 295 22261031
2011 Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood 196 21865341
2015 TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Science translational medicine 165 26446955
2014 Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression. Cell cycle (Georgetown, Tex.) 99 25485578
2011 Bortezomib induces nuclear translocation of IκBα resulting in gene-specific suppression of NF-κB--dependent transcription and induction of apoptosis in CTCL. Molecular cancer research : MCR 85 21224428
1982 Clinical implications of cytogenetic studies in cutaneous T-cell lymphoma (CTCL). Cancer 84 6981450
2016 Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB. Blood 80 27268084
2017 Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy. Cancer 77 28493286
2008 Low FAS/CD95 expression by CTCL correlates with reduced sensitivity to apoptosis that can be restored by FAS upregulation. The Journal of investigative dermatology 77 18923451
2001 SET-related cell division autoantigen-1 (CDA1) arrests cell growth. The Journal of biological chemistry 75 11395479
2006 Quantitative PCR on 5 genes reliably identifies CTCL patients with 5% to 99% circulating tumor cells with 90% accuracy. Blood 70 16403914
2015 The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL). Clinical cancer research : an official journal of the American Association for Cancer Research 67 25779945
2018 Cryptococcus neoformans Cda1 and Its Chitin Deacetylase Activity Are Required for Fungal Pathogenesis. mBio 65 30459196
2000 Expression of Fas and Fas-ligand in primary cutaneous T-cell lymphoma (CTCL): association between lack of Fas expression and aggressive types of CTCL. The British journal of dermatology 65 10951138
2015 Improved pruritus correlates with lower levels of IL-31 in CTCL patients under different therapeutic modalities. Clinical immunology (Orlando, Fla.) 64 25762519
2011 High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade. Blood 63 21209378
2022 Macrophage-derived CXCL9 and CXCL11, T-cell skin homing, and disease control in mogamulizumab-treated CTCL patients. Blood 61 34905599
2014 Analysis of STAT4 expression in cutaneous T-cell lymphoma (CTCL) patients and patient-derived cell lines. Cell cycle (Georgetown, Tex.) 60 25486484
2007 Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. The Journal of biological chemistry 59 17317670
1996 T-cell lymphoma cell lines (HUT102 and HUT78) established at the National Cancer Institute: history and importance to understanding the biology, clinical features, and therapy of cutaneous T-cell lymphomas (CTCL) and adult T-cell leukemia-lymphomas (ATLL). Journal of cellular biochemistry. Supplement 54 8806090
2001 Identification of differentially expressed nucleolar TGF-beta1 target (DENTT) in human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily. Genomics 52 11318608
2015 Romidepsin and Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL. Clinical cancer research : an official journal of the American Association for Cancer Research 51 26660520
2019 Environmental and Other Extrinsic Risk Factors Contributing to the Pathogenesis of Cutaneous T Cell Lymphoma (CTCL). Frontiers in oncology 49 31106143
2007 Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat. Biologics : targets & therapy 48 19707308
2018 TSPYL2 is a novel regulator of SIRT1 and p300 activity in response to DNA damage. Cell death and differentiation 47 30050056
2017 Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1 leukemic cell lines. Oncotarget 46 29221181
2011 Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells. PloS one 46 21949767
2015 Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders. European journal of human genetics : EJHG 44 26059843
2003 Expression of apoptosis regulators in cutaneous T-cell lymphoma (CTCL) cells. The Journal of pathology 44 12754746
2017 Distribution and Clustering of Cutaneous T-Cell Lymphoma (CTCL) Cases in Canada During 1992 to 2010. Journal of cutaneous medicine and surgery 43 29241349
2019 Systemic therapy of cutaneous T-cell lymphoma (CTCL). Chinese clinical oncology 38 30818958
2014 Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sézary syndrome). Annals of oncology : official journal of the European Society for Medical Oncology 38 24948692
2016 Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction. Journal of the American Academy of Dermatology 37 26874819
2015 TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation. Cell death and differentiation 36 25613376
2011 TSPYL2 is important for G1 checkpoint maintenance upon DNA damage. PloS one 36 21738728
2005 cda1+, encoding chitin deacetylase is required for proper spore formation in Schizosaccharomyces pombe. FEBS letters 36 15862318
2016 Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy. Oncoimmunology 35 27622024
2020 A Small Molecule CCR2 Antagonist Depletes Tumor Macrophages and Synergizes with Anti-PD-1 in a Murine Model of Cutaneous T-Cell Lymphoma (CTCL). The Journal of investigative dermatology 34 31945344
2008 Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) exhibits an inhibitory role on tumorigenesis. Carcinogenesis 34 18381359
2018 Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study. Clinical pharmacology and therapeutics 33 29377077
2016 Second Primary Malignancies in CTCL Patients from 1992 to 2011: A SEER-Based, Population-Based Study Evaluating Time from CTCL Diagnosis, Age, Sex, Stage, and CD30+ Subtype. American journal of clinical dermatology 31 26386881
2009 Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells. Blood 31 19211505
2016 TOX expression and role in CTCL. Journal of the European Academy of Dermatology and Venereology : JEADV 29 27345620
2020 JAK inhibition synergistically potentiates BCL2, BET, HDAC, and proteasome inhibition in advanced CTCL. Blood advances 28 32437546
1995 Basaloid folliculolymphoid hyperplasia with alopecia as an expression of mycosis fungoides (CTCL). Journal of cutaneous pathology 28 8594081
2020 Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo. Oncotarget 27 32284791
2019 Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in erythrodermic cutaneous T-cell lymphoma (CTCL) patients. Archives of dermatological research 27 31776647
1997 Proceedings of the International Consensus Conference on Cutaneous T-cell Lymphoma (CTCL) Treatment Recommendations. Boston, Massachusetts, Oct. 1 and 2, 1994. Journal of the American Academy of Dermatology 27 9091480
2007 Identification of selectively expressed genes and antigens in CTCL. Experimental dermatology 26 17979976
1997 CTCL in patients under 20 years of age: a series of five cases. Pediatric dermatology 26 9144692
2018 Diabetes Reduces Severity of Aortic Aneurysms Depending on the Presence of Cell Division Autoantigen 1 (CDA1). Diabetes 24 29311219
2020 Risk of bacteremia in patients with cutaneous T-cell lymphoma (CTCL). Leukemia & lymphoma 22 32558600
2018 Cutaneous T-cell lymphoma (CTCL), rare subtypes: five case presentations and review of the literature. Chinese clinical oncology 21 30525759
2007 Molecular cytogenetics in the study of cutaneous T-cell lymphomas (CTCL). Cytogenetic and genome research 21 18000390
1996 T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin. Journal of cutaneous pathology 21 8864915
1994 Impact of non-CTCL dermatologic diagnoses and adjuvant therapies on cutaneous T-cell lymphoma patients treated with total skin electron beam radiation therapy. International journal of radiation oncology, biology, physics 21 8138435
2021 JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL). Cancers 20 33466582
2018 Heterologous expression, characterization and possible functions of the chitin deacetylases, Cda1 and Cda2, from mushroom Coprinopsis cinerea. Glycobiology 20 29370398
2018 A study of meiomitosis and novel pathways of genomic instability in cutaneous T-cell lymphomas (CTCL). Oncotarget 20 30701021
2017 TCR-CXCR4 signaling stabilizes cytokine mRNA transcripts via a PREX1-Rac1 pathway: implications for CTCL. Blood 20 28694325
2010 Structural alterations of the FAS gene in cutaneous T-cell lymphoma (CTCL). Archives of biochemistry and biophysics 20 21036138
2000 Historical perspective on the use of retinoids in cutaneous T-cell lymphoma (CTCL). Clinical lymphoma 19 11707863
2023 CRL2APPBP2-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence. Science China. Life sciences 18 38170390
2019 Management of mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL): focus on chlormethine gel. Cancer management and research 18 30962713
2005 Differentially expressed nucleolar TGF-beta1 target (DENTT) shows tissue-specific nuclear and cytoplasmic localization and increases TGF-beta1-responsive transcription in primates. Biochimica et biophysica acta 18 15823505
2023 AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-β signaling in mice. Cell death & disease 17 37391440
2019 Investigative drugs for the treatment of cutaneous T-cell lymphomas (CTCL): an update. Expert opinion on investigational drugs 17 31398295
2018 Targeting the CDA1/CDA1BP1 Axis Retards Renal Fibrosis in Experimental Diabetic Nephropathy. Diabetes 17 30425061
2016 Identification of a homozygous missense mutation in LRP2 and a hemizygous missense mutation in TSPYL2 in a family with mild intellectual disability. Psychiatric genetics 17 26529358
2015 A novel targeted immunotherapy for CTCL is on its way: Anti-KIR3DL2 mAb IPH4102 is potent and safe in non-clinical studies. Oncoimmunology 17 26405593
2010 Absence of modulation of CD4+CD25 regulatory T cells in CTCL patients treated with bexarotene. Experimental dermatology 17 19845755
2022 TSPYL2 reduced gefitinib resistance and DNA damage repair via suppressing SIRT1-mediated FOXO3 deacetylation. Future medicinal chemistry 16 35192400
2019 The Ectopic Expression of Meiosis Regulatory Genes in Cutaneous T-Cell Lymphomas (CTCL). Frontiers in oncology 16 31214493
2014 The nucleosome assembly protein TSPYL2 regulates the expression of NMDA receptor subunits GluN2A and GluN2B. Scientific reports 16 24413569
2007 Systemic monotherapy vs combination therapy for CTCL: rationale and future strategies. Oncology (Williston Park, N.Y.) 16 17474358
2003 Differentially expressed nucleolar TGF-beta1 target (DENTT) in mouse development. Developmental dynamics : an official publication of the American Association of Anatomists 16 12619135
2007 Proteomic patterns for classification of ovarian cancer and CTCL serum samples utilizing peak pairs indicative of post-translational modifications. Proteomics 15 17952875
2004 Heterozygote AG variant of -596 A/G IL-6 gene polymorphism is a marker for cutaneous T-cell lymphoma (CTCL). Clinical immunology (Orlando, Fla.) 15 15507390
2006 Future perspectives in the treatment of cutaneous T-cell lymphoma (CTCL). Seminars in oncology 14 16516674
2002 Expression of differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) in adult mouse tissues. Developmental dynamics : an official publication of the American Association of Anatomists 14 12112471
2022 The Skin Microbiome in Cutaneous T-Cell Lymphomas (CTCL)-A Narrative Review. Pathogens (Basel, Switzerland) 13 36015055
2021 Ginsenoside Rg3 increases gemcitabine sensitivity of pancreatic adenocarcinoma via reducing ZFP91 mediated TSPYL2 destabilization. Journal of ginseng research 13 36090681
2019 Antibody-Directed Therapies: Toward a Durable and Tolerable Treatment Platform for CTCL. Frontiers in oncology 13 31417860
2023 CCR4-IL2 bispecific immunotoxin is more effective than brentuximab for targeted therapy of cutaneous T-cell lymphoma in a mouse CTCL model. FEBS open bio 12 37157185
2018 Epigenetic therapy and dermatologic disease: moving beyond CTCL. The Journal of dermatological treatment 12 29726727
2018 TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons. Molecular neurobiology 12 30051352
2010 About the cutaneous targets of bexarotene in CTCL patients. Experimental dermatology 12 19845753
2010 Role of Cell Division Autoantigen 1 (CDA1) in Cell Proliferation and Fibrosis. Genes 12 24710090
2006 Biological insights into the pathogenesis of cutaneous T-cell lymphomas (CTCL). Seminars in oncology 12 16516668
2006 Therapeutic advances in cutaneous T-cell lymphoma (CTCL): from retinoids to rexinoids. Seminars in oncology 12 16516669
2024 The role of stem cell transplant (auto and allo) in PTCL and CTCL. Hematology. American Society of Hematology. Education Program 11 39644016
2021 The Role of Cell Division Autoantigen 1 (CDA1) in Renal Fibrosis of Diabetic Nephropathy. BioMed research international 11 33997036
2021 Contemporary Treatment Patterns and Response in Relapsed/Refractory Cutaneous T-Cell Lymphoma (CTCL) across Five European Countries. Cancers 11 35008309
2018 Mogamulizumab Tops Standard of Care for CTCL. Cancer discovery 10 29298770
2016 Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice. Behavior genetics 10 26826030
2015 ALK-positive primary cutaneous T-cell-lymphoma (CTCL) with unusual clinical presentation and aggressive course. Journal of cutaneous pathology 10 26053561
1990 Treatment of cutaneous T-cell lymphomas (CTCL) with extracorporeal photochemotherapy--preliminary report. The Journal of dermatology 10 2086618
2023 A tumor-suppressing role of TSPYL2 in thyroid cancer: Through interacting with SIRT1 and repressing SIRT1/AKT pathway. Experimental cell research 9 37696385
2014 Analysis of TGFβ1 and IL-10 transcriptional regulation in CTCL cells by chromatin immunoprecipitation. Methods in molecular biology (Clifton, N.J.) 9 24908319

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