Affinage

BTG2

Protein BTG2 · UniProt P78543

Length
158 aa
Mass
17.4 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BTG2 is an antiproliferative transcriptional co-regulator and mRNA decay factor that couples cell cycle arrest to differentiation across multiple tissues. Transcriptionally induced by p53 in response to DNA damage (PMID:8944033, PMID:11814693), BTG2 enforces G1 arrest primarily by repressing cyclin D1 transcription through promoter-associated histone deacetylation (PMID:15056715, PMID:17371797) and by recruiting PRMT1 to methylate CDK4, thereby blocking CDK4–Cyclin D3 complex formation (PMID:28628091). BTG2 also functions as a general activator of mRNA deadenylation through its conserved box B–mediated interaction with the CAF1/POP2 subunits of the CCR4-NOT complex, promoting poly(A) shortening and transcript turnover that maintains quiescence in T cells and restrains cardiomyocyte hypertrophy (PMID:18337750, PMID:32165587, PMID:27346836). Beyond cell cycle control, BTG2 serves as a context-dependent transcriptional co-regulator—co-repressing androgen receptor via its LxxLL motif (PMID:21172304), co-activating NFE2L2/NRF2-driven antioxidant gene expression (PMID:22493435), and modulating PRMT1-dependent histone H4 arginine methylation at retinoic acid receptor target promoters during myeloid differentiation (PMID:16782888).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    BTG2 was identified as a p53-target gene induced by DNA damage, establishing it as a previously unknown effector linking the p53 response to cell cycle inhibition.

    Evidence Cloning and p53-dependent transcriptional induction assays in rodent and human cells

    PMID:8944033

    Open questions at the time
    • Mechanism of cell cycle arrest was unknown
    • Direct p53 binding element not yet mapped
  2. 1998 High

    Two key mechanistic advances revealed that BTG2 physically interacts with the CCR4-associated factor CAF1 through its conserved box B domain and that overexpression causes G1 arrest by reducing cyclin E and CDK4 levels, framing BTG2 as both a transcriptional complex participant and a G1-S checkpoint enforcer.

    Evidence Yeast two-hybrid, Co-IP and domain mutagenesis for CAF1 binding; FACS, Western blot and kinase assays for cell cycle effects in 293 cells

    PMID:9712883 PMID:9766435

    Open questions at the time
    • Whether BTG2-CAF1 interaction mediates deadenylation versus transcription was unresolved
    • Cyclin D1 regulation not yet examined
  3. 2002 High

    Mapping of the p53 response element in the BTG2 promoter demonstrated direct transcriptional control of BTG2 by p53, solidifying the upstream activation mechanism.

    Evidence Promoter deletion/mutagenesis, EMSA, and reporter assays

    PMID:11814693

    Open questions at the time
    • Other transcriptional inputs to BTG2 (e.g. NF-κB) not yet examined
  4. 2003 High

    Demonstration that BTG2 exists in vivo within human CCR4-containing complexes whose composition and localization change during the cell cycle extended the initial yeast two-hybrid finding to a physiological context.

    Evidence Reciprocal Co-IP, gel filtration, and transcriptional reporter assays in mammalian cells

    PMID:12771185

    Open questions at the time
    • Enzymatic consequences of BTG2 on CCR4-NOT deadenylase activity not yet tested
  5. 2004 High

    ChIP and transgenic mouse studies showed that BTG2 represses cyclin D1 transcription by binding its promoter and promoting local histone deacetylation, providing the specific transcriptional mechanism underlying G1 arrest and linking it to medulloblastoma suppression in vivo.

    Evidence ChIP at cyclin D1 promoter, histone deacetylation assays, Patched1-heterozygous transgenic mice

    PMID:15056715 PMID:15378000 PMID:17371797

    Open questions at the time
    • Identity of HDAC recruited by BTG2 was not determined
    • Whether cyclin D1 repression is the sole anti-tumor mechanism remained unclear
  6. 2006 High

    Discovery that BTG2 recruits PRMT1 to the RARα complex at the RARβ promoter, modulating histone H4 arginine methylation and controlling myeloid differentiation, established BTG2 as a chromatin-modifying co-regulator beyond simple transcriptional repression.

    Evidence Co-IP, ChIP on RARβ promoter, histone modification assays in hematopoietic cells and CD34+ progenitors

    PMID:16782888

    Open questions at the time
    • Whether PRMT1 recruitment is relevant at other BTG2-regulated promoters was unknown
    • Mechanism of RA-induced cytoplasmic relocalization unclear
  7. 2008 High

    Reconstituted in vitro assays and crystal structures of BTG2 established that BTG2 is a general activator of CAF1/CCR4-dependent mRNA deadenylation, shifting the model from a purely transcriptional regulator to a dual transcription/mRNA decay factor.

    Evidence X-ray crystallography (2.2–2.3 Å), in vitro deadenylation assays with wild-type and mutant BTG2/CAF1, multiple transcript substrates

    PMID:18337750 PMID:18974182

    Open questions at the time
    • Transcript selectivity of BTG2-stimulated deadenylation was not addressed
    • In vivo global mRNA effects awaited genetic models
  8. 2009 High

    BTG2-null mice revealed roles in adult neurogenesis—progenitor over-proliferation and failed terminal differentiation—with ChIP evidence that BTG2 directly represses the Id3 promoter, identifying a key downstream target in the differentiation program.

    Evidence Tis21-knockout mice, BrdU labeling, immunohistochemistry, ChIP at Id3 promoter

    PMID:19263516 PMID:20020054

    Open questions at the time
    • Relationship between Id3 repression and deadenylation function was unresolved
    • Whether BTG2 governs all Id family members unclear
  9. 2010 High

    Identification of BTG2 as an LxxLL motif-dependent co-repressor of the androgen receptor broadened its repertoire from p53/RARα co-regulation to nuclear receptor co-repression relevant to prostate cancer.

    Evidence Co-IP, LxxLL mutagenesis, AR reporter assays, proliferation assays in prostate cancer cells

    PMID:21172304

    Open questions at the time
    • Whether AR co-repression involves PRMT1 or CAF1 recruitment was not tested
  10. 2012 High

    BTG2 was shown to co-activate NFE2L2/NRF2 at antioxidant response elements via box B-dependent physical interaction, establishing a previously unrecognized function in oxidative stress defense.

    Evidence Co-IP, ChIP at AREs, mutagenesis, siRNA knockdown, ROS assays in mammary epithelial cells

    PMID:22493435

    Open questions at the time
    • Whether NRF2 co-activation is independent of deadenylation activity is unknown
  11. 2014 Medium

    Mouse genetic models showed that BTG2 dosage is tightly controlled: excess BTG2 protein (via 3ʹ-UTR deletion, removing miR-92-dependent repression) causes microcephaly by premature symmetric progenitor divisions, while loss of BTG2 disrupts BMP4/Smad signaling and blocks neuroblast differentiation.

    Evidence Tis21 3ʹ-UTR-knockout mice (neocortex), Tis21-KO SVZ analysis, miR-92 functional assays, BMP4/siRNA rescue experiments

    PMID:24726360 PMID:24744701

    Open questions at the time
    • Whether the miR-92–BTG2 axis operates outside neocortical development is untested
    • Direct link between BTG2 and BMP4 transcriptional activation not shown
  12. 2017 High

    Discovery that the BTG2-PRMT1 module methylates CDK4, preventing CDK4–Cyclin D3 complex formation, provided a non-transcriptional post-translational mechanism for cell cycle arrest and showed therapeutic relevance in blocking BCR-ABL1+ pre-B cell leukemia.

    Evidence In vitro CDK4 methylation assay, Co-IP, genetic loss-of-function, in vivo leukemia model

    PMID:28628091

    Open questions at the time
    • The specific CDK4 arginine residue(s) methylated were not fully mapped in this study
    • Whether CDK4 methylation occurs in non-hematopoietic contexts is unknown
  13. 2020 High

    Conditional BTG1/BTG2 double-knockout T cells demonstrated that BTG-family-mediated mRNA deadenylation globally maintains T cell quiescence by enforcing short poly(A) tails and rapid transcript turnover, validating the in vitro deadenylation activity at a systems level in vivo.

    Evidence Double-KO mice, global mRNA abundance and poly(A) tail measurements, T cell activation assays

    PMID:32165587

    Open questions at the time
    • Relative contributions of BTG1 vs BTG2 individually were not fully separated
    • Whether specific mRNA subsets are preferentially regulated is not resolved
  14. 2020 Medium

    TRIM6 was identified as the E3 ubiquitin ligase that ubiquitinates BTG2 at Lys5, governing BTG2 protein stability, which explained how BTG2 protein levels are post-translationally tuned to regulate FoxM1-dependent proliferation in colorectal cancer.

    Evidence Ubiquitination assay, TRIM6 catalytic mutant, BTG2 K5 mutagenesis, proliferation assays

    PMID:31992359

    Open questions at the time
    • Whether other E3 ligases also target BTG2 is unknown
    • Deubiquitinase for BTG2 not identified
  15. 2022 Medium

    KIAA1429/VIRMA-mediated m6A methylation of BTG2 mRNA leads to YTHDF2-dependent degradation, revealing an epitranscriptomic layer of BTG2 regulation exploited in lung adenocarcinoma.

    Evidence MeRIP-seq, RNA immunoprecipitation, mRNA stability assays, siRNA knockdown

    PMID:35730068

    Open questions at the time
    • Specific m6A sites on BTG2 mRNA not mapped at nucleotide resolution
    • Whether m6A-mediated BTG2 suppression occurs in normal tissues is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: what determines transcript selectivity of BTG2-stimulated deadenylation, the structural basis of the BTG2-PRMT1-CDK4 ternary complex, whether the transcriptional co-regulator and mRNA decay functions are mechanistically coupled or independent, and the full repertoire of E3 ligases and deubiquitinases governing BTG2 protein stability.
  • Transcript selectivity mechanism for deadenylation unknown
  • No structural model of BTG2-PRMT1-CDK4 complex
  • Independence vs coupling of transcriptional and deadenylation functions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 3
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3 R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 2 R-HSA-168256 Immune System 1
Partners
ARCNOT7CNOT8NFE2L2PRMT1SMAD3TP53TRIM6
Complex memberships
CCR4-NOT

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 BTG2 expression is induced through a p53-dependent mechanism in response to DNA damage, and BTG2 function is relevant to cell cycle control, identifying it as an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Cloning, transfection, and p53-dependent transcriptional induction assays in rodent and human cells Nature genetics High 8944033
1998 BTG2 (and BTG1) physically interact in vitro and in vivo with mCaf1 (mouse CCR4-associated factor 1), a component of the yeast CCR4 transcriptional regulatory complex, via the conserved box B domain; this interaction suggests BTG proteins participate in transcriptional regulation of cell cycle genes. Yeast two-hybrid screening, protein-binding assays, transient transfection in HeLa cells, domain mutagenesis The Journal of biological chemistry High 9712883
1998 TIS21/BTG2 overexpression in 293 cells causes G1 accumulation associated with reduced synthesis of cyclin E and CDK4, and decreased cyclin E-associated CDK activity, demonstrating that BTG2 inhibits G1-S progression by downregulating these cell cycle regulators. Stable transfection, FACS cell cycle analysis, Western blot for cyclin E and CDK4, CDK kinase activity assay Molecular carcinogenesis High 9766435
2003 BTG2 interacts in vivo with the human CCR4 complex (hCCR4 via hCAF1 and hPOP2) in mammalian cells; the CCR4-containing complexes exist in cell-cycle-regulated forms and hCAF1 localization changes as cells progress from quiescence to S phase. Immunoprecipitation, gel filtration, transcriptional reporter assays Journal of cell science High 12771185
2004 PC3/BTG2 represses cyclin D1 transcription by recruiting itself to the cyclin D1 promoter with associated histone deacetylation, thereby inducing G1 arrest in cerebellar granule precursors and inhibiting medulloblastoma development. Transgenic mouse models, chromatin immunoprecipitation (ChIP), cyclin D1 promoter assays, histone deacetylation analysis The Journal of neuroscience High 15056715
2006 BTG2 is present in the RARα transcriptional complex together with PRMT1 and Sin3A; BTG2 overexpression increases PRMT1 participation in the RARα complex on the RARβ promoter, enhancing gene-specific histone H4 arginine methylation, and upon RA treatment BTG2 and PRMT1 move to the cytoplasm, enabling histone H4 demethylation and acetylation that promote myeloid differentiation. Co-immunoprecipitation, ChIP on RARβ promoter, histone modification assays, overexpression in hematopoietic cells and CD34+ progenitors Molecular and cellular biology High 16782888
2007 PC3/BTG2 recruitment to the cyclin D1 promoter is accompanied by histone deacetylation; overexpression of PC3 in cerebellar granule precursors inhibits cyclin D1 expression and medulloblastoma incidence in Patched1 heterozygous mice. ChIP, transgenic mouse crosses (TgPC3 × Ptc+/-), cyclin D1 promoter analysis, histology FASEB journal High 17371797
2008 BTG2 is a general activator of mRNA deadenylation: it enhances deadenylation of all transcripts tested through interaction with the CAF1/POP2 deadenylase, requires CAF1 nuclease activity, and depends on deadenylase activities of both CAF1 and CCR4 for efficient poly(A) degradation. In vitro deadenylation assays, mutagenesis of BTG2 and CAF1, mRNA stability assays in mammalian cells The EMBO journal High 18337750
2008 Crystal structures of human BTG2 and mouse TIS21 at 2.3 Å and 2.2 Å resolution reveal the putative CAF1-binding site; BTG2 mutations disrupting the CAF1-binding interface suppress CAF1 deadenylase activity, demonstrating a suppressive role for BTG2 in CAF1 deadenylase regulation. X-ray crystallography, CAF1 deadenylase assays with wild-type and mutant BTG2 Nucleic acids research High 18974182
2009 PC3/Tis21-null mice show increased proliferation of progenitor cells in the adult dentate gyrus, arrest of terminal differentiation, and accumulation of undifferentiated post-mitotic neurons; BTG2 associates with the Id3 promoter and negatively regulates Id3 expression, acting upstream of this inhibitor of proneural gene activity. Knockout mouse model, BrdU labeling, immunohistochemistry, ChIP on Id3 promoter, behavioral testing (contextual memory) PloS one High 20020054
2010 BTG2 directly binds to androgen receptor (AR) via its LxxLL motif at positions 92-96 (but not 20-24); BTG2 acts as an LXXLL-dependent co-repressor of AR transcriptional activity and suppresses PSA promoter activation and prostate cancer cell growth. Co-immunoprecipitation, LxxLL motif mutagenesis, AR transcriptional reporter assays, cell proliferation assays Biochemical and biophysical research communications High 21172304
2012 BTG2 protects human mammary epithelial cells from oxidative stress by acting as a binding partner for NFE2L2 (NRF2), increasing NFE2L2 transcriptional activity, upregulating antioxidant enzymes (catalase, SOD1, SOD2), and being detectable at antioxidant response elements; box B motif is required for these activities. Co-immunoprecipitation, ChIP at ARE, oxidative stress assays, box B mutagenesis, siRNA knockdown of NFE2L2 The Journal of biological chemistry High 22493435
2017 The BTG2-PRMT1 module induces cell-cycle arrest in pre-B cells; PRMT1 methylates CDK4, thereby preventing formation of the CDK4-Cyclin-D3 complex and blocking cell cycle progression; BTG2 with PRMT1 efficiently blocked proliferation of BCR-ABL1-transformed pre-B cells. Proteomics, immunoprecipitation, in vitro methylation assay of CDK4 by PRMT1, genetic loss-of-function, in vivo leukemia model Nature immunology High 28628091
2020 BTG1 and BTG2 together maintain T cell quiescence by promoting deadenylation and degradation of mRNA; BTG1/2-deficient T cells show globally increased mRNA abundance with longer poly(A) tails and increased mRNA half-life, lowering the threshold for T cell activation. Conditional double knockout mice, global mRNA abundance measurement, poly(A) tail length analysis, proliferation and activation assays Science High 32165587
2013 TIS21/BTG2 inhibits IL-6 expression in human dermal fibroblasts by inhibiting JAK2-STAT3 signaling through suppression of ROS generation; BTG2 is localized to mitochondria where it exerts this inhibitory effect on STAT3 phosphorylation. Adenoviral gene transduction, siRNA knockdown, STAT3 ChIP on IL-6 promoter, ROS measurement, mitochondrial localization assay Cellular signalling Medium 23917204
2016 TIS21/BTG2 shifts p53-induced senescence to apoptosis by modulating post-translational modification of p53 (Ser-15 and Ser-46 phosphorylation; Lys-120, -320, -373, -382 acetylation), and by enhancing miR34a and Bax expression while inhibiting SIRT1 and the p53-iASPP interaction. Adenoviral transduction of p53 and TIS21, Western blot for p53 modifications, co-immunoprecipitation (p53-iASPP), siRNA knockdown Cellular signalling Medium 27208501
2016 BTG2 negatively regulates cardiomyocyte hypertrophy by suppressing cytosolic (but not nuclear) RNA levels through binding to mRNA deadenylation complexes; Btg2 knockdown enhances cytosolic RNA accumulation and adrenergic stimulus-induced hypertrophy. Mass spectrometry identification of BTG2 binding partners (deadenylation complexes), shRNA knockdown, single-cell RNA imaging, ChIP-seq for Myc targets, cardiomyocyte surface area measurement Scientific reports Medium 27346836
2016 TIS21/BTG2 negatively regulates expansions of hematopoietic stem cells (LSK cells) in female mice by inhibiting estradiol-induced mTOR activation; TIS21 inhibits the interaction between Akt and phosphorylated Erk1/2, preventing constitutive mTOR activation, as shown by immunoprecipitation experiments. TIS21 knockout mice, immunoprecipitation (Akt-pErk1/2 interaction), MEF culture, Akt/mTOR Western blot, reconstitution with TIS21 Stem cells Medium 18556508
2014 The Tis21 (BTG2) 3' UTR is required to restrict Tis21 protein levels via miR-92-dependent post-transcriptional regulation; mice lacking the Tis21 3' UTR develop microcephalic neocortex due to apical progenitors prematurely switching from asymmetric to symmetric self-consuming divisions caused by excess Tis21 protein. Tis21 3'-UTR knockout mice, neocortex size measurement, progenitor division analysis, miR-92 functional assays Cell reports Medium 24726360
2014 Tis21/BTG2 in the subventricular zone activates BMP4/Smad1/8 signaling and inhibits the Notch pathway (Hes1/5) and cell cycle cyclins; loss of Tis21 leads to Id1-3 upregulation and accumulation of undifferentiated neuroblasts that fail to migrate to the olfactory bulb; Id3 silencing or BMP4 addition rescues differentiation in Tis21-null neurospheres. Tis21 knockout mice, neurosphere culture, qRT-PCR for BMP4/Smad/Hes/Id/NeuroD1, BMP4 rescue, siRNA Id3, behavioral olfactory testing Frontiers in cellular neuroscience Medium 24744701
2009 Nuclear DGK-zeta upregulates TIS21/BTG2 expression and downregulates cyclin D1; TIS21/BTG2 overexpression mimics DGK-zeta-mediated G1 arrest with decreased Rb phosphorylation; siRNA knockdown of TIS21/BTG2 impairs myogenic differentiation of C2C12 cells by opposing cell cycle arrest. DNA microarray, RT-PCR, Western blot, siRNA knockdown, cell cycle analysis, overexpression in C2C12 myoblasts Cellular signalling Medium 19263516
2020 TRIM6 promotes ubiquitination of TIS21/BTG2 at Lys5, reducing BTG2 protein stability; TRIM6 E3 catalytic mutant (C15A) fails to ubiquitinate BTG2; loss of BTG2 stabilization by TRIM6 results in increased FoxM1 signaling and enhanced CRC cell proliferation. Immunoprecipitation, proteomics, ubiquitination assay, TRIM6 E3 mutant, BTG2 Lys5 mutagenesis, Western blot, CRC cell proliferation assays Journal of experimental & clinical cancer research Medium 31992359
2021 BTG2 promotes podocyte-mesenchymal transition (EMT) in focal segmental glomerulosclerosis via binding to Smad3 (but not Smad2), potentiating TGF-β/Smad3 signaling; podocyte-specific deletion of BTG2 protects against ADR-induced FSGS; Smad3 inhibitor also suppresses BTG2 expression, revealing a TGF-β/Smad3-BTG2 positive circuit. Podocyte-specific BTG2 knockout mice, Co-immunoprecipitation (BTG2-Smad3/Smad2), overexpression/knockdown in MPC5 podocytes, ADR model, Smad3 inhibitor SIS3 Advanced science Medium 37749872
2021 Growth hormone promotes hepatic gluconeogenesis via BTG2-YY1 signaling: BTG2 and YY1 induce PCK1 and G6PC expression; YY1 directly binds the Pck1 and G6pc gene promoters (identified by reporter assays and point mutation analysis); knockdown of Btg2 and Yy1 diminishes GH-induced glucose production. Primary mouse hepatocytes, mouse liver overexpression/knockdown, reporter assays, YY1 promoter point mutation analysis, glucose production assay Scientific reports Medium 34556771
2022 KIAA1429 (VIRMA) promotes m6A methylation of BTG2 mRNA, leading to YTHDF2-dependent BTG2 mRNA degradation; knockdown of KIAA1429 decreases BTG2 mRNA m6A levels and enhances BTG2 mRNA stability, restoring BTG2 expression in lung adenocarcinoma. MeRIP-seq, RNA immunoprecipitation (RIP), RNA stability assay, transcriptome sequencing, siRNA knockdown Cancer communications Medium 35730068
2004 NF-κB activates BTG2 expression in breast cancer cells; ectopic BTG2 expression arrests breast cancer cells in G1, an effect reversed by cyclin D1; BTG2 suppresses cyclin D1, consistent with its G1 arrest mechanism. NF-κB inhibitors, BTG2 overexpression, FACS cell cycle analysis, cyclin D1 rescue experiments Oncogene Medium 15378000
2002 The BTG2 gene has a major wild-type p53 response element located -74 to -122 relative to the start codon; mutation of this element abolishes p53-induced BTG2 promoter activity, demonstrating direct transcriptional regulation of BTG2 by p53. Promoter deletion analysis, transient transfection reporter assays, EMSA, site-directed mutagenesis of p53 response element Gene High 11814693

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Nature genetics 379 8944033
2011 PC3 is a cell line characteristic of prostatic small cell carcinoma. The Prostate 375 21432867
2001 In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS letters 216 11377414
2001 The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair? Journal of cellular physiology 196 11267995
2012 Androgen-regulated miR-32 targets BTG2 and is overexpressed in castration-resistant prostate cancer. Oncogene 176 22266859
1999 Expression of the antiproliferative gene TIS21 at the onset of neurogenesis identifies single neuroepithelial cells that switch from proliferative to neuron-generating division. Proceedings of the National Academy of Sciences of the United States of America 169 10200315
2018 Tumor suppressors BTG1 and BTG2: Beyond growth control. Journal of cellular physiology 161 30350856
2009 Regulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma. Cell research 153 19546886
2020 mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence. Science (New York, N.Y.) 142 32165587
1998 Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complex. The Journal of biological chemistry 125 9712883
2016 MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2. Oncotarget 118 27409164
2018 MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Molecular cancer 112 29310680
2008 The BTG2 protein is a general activator of mRNA deadenylation. The EMBO journal 107 18337750
2006 TIS21 (/BTG2/PC3) as a link between ageing and cancer: cell cycle regulator and endogenous cell death molecule. Journal of cancer research and clinical oncology 90 16456675
2015 MiR-21 Protected Cardiomyocytes against Doxorubicin-Induced Apoptosis by Targeting BTG2. International journal of molecular sciences 85 26132560
2009 Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. Molecular cancer therapeutics 77 19509250
2004 Dual control of neurogenesis by PC3 through cell cycle inhibition and induction of Math1. The Journal of neuroscience : the official journal of the Society for Neuroscience 75 15056715
2009 Impaired terminal differentiation of hippocampal granule neurons and defective contextual memory in PC3/Tis21 knockout mice. PloS one 72 20020054
1998 Induction of growth inhibition of 293 cells by downregulation of the cyclin E and cyclin-dependent kinase 4 proteins due to overexpression of TIS21. Molecular carcinogenesis 68 9766435
2004 Expression of the NF-kappaB-responsive gene BTG2 is aberrantly regulated in breast cancer. Oncogene 65 15378000
1996 Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice. Invasion & metastasis 64 9186547
2022 Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma. Cancer communications (London, England) 61 35730068
2002 The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene. Gene 60 11814693
2007 Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 59 17371797
2003 BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms. Journal of cell science 58 12771185
2006 Btg2 enhances retinoic acid-induced differentiation by modulating histone H4 methylation and acetylation. Molecular and cellular biology 57 16782888
2001 Effect of scopoletin on PC3 cell proliferation and apoptosis. Acta pharmacologica Sinica 55 11749777
2021 m6A-Induced LncRNA MEG3 Suppresses the Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cell Through miR-544b/BTG2 Signaling. OncoTargets and therapy 53 34163177
2009 Impact of BTG2 expression on proliferation and invasion of gastric cancer cells in vitro. Molecular biology reports 49 19728149
2019 MiR-6875-3p promotes the proliferation, invasion and metastasis of hepatocellular carcinoma via BTG2/FAK/Akt pathway. Journal of experimental & clinical cancer research : CR 46 30621734
2002 PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis. Neuroreport 45 11930152
2017 The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex. Nature immunology 44 28628091
2008 Crystal structures of human BTG2 and mouse TIS21 involved in suppression of CAF1 deadenylase activity. Nucleic acids research 42 18974182
2003 The prohormone processing enzyme PC3 is a lipid raft-associated transmembrane protein. Biochemistry 41 12950171
2020 Beneficial effects of genistein in suppression of proliferation, inhibition of metastasis, and induction of apoptosis in PC3 prostate cancer cells. Archives of physiology and biochemistry 39 31985311
2020 SRXN1 stimulates hepatocellular carcinoma tumorigenesis and metastasis through modulating ROS/p65/BTG2 signalling. Journal of cellular and molecular medicine 39 32746503
2017 BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells. Cancer medicine 39 29239139
2004 BTG2, its family and its tutor. Bulletin du cancer 39 15381462
1999 Melatonin receptors in PC3 human prostate tumor cells. Journal of pineal research 39 10340723
2022 Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p/PTEN. Cell death & disease 38 35643814
2014 3' UTR-dependent, miR-92-mediated restriction of Tis21 expression maintains asymmetric neural stem cell division to ensure proper neocortex size. Cell reports 38 24726360
2012 Cell killing and radiosensitizing effects of atorvastatin in PC3 prostate cancer cells. Journal of radiation research 38 22510595
2000 PC3 overexpression affects the pattern of cell division of rat cortical precursors. Mechanisms of development 37 10585559
2022 Emerging role of anti-proliferative protein BTG1 and BTG2. BMB reports 36 35880434
2016 MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features. Oncotarget 36 27248169
2020 TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1. Journal of experimental & clinical cancer research : CR 34 31992359
2015 miR-25 modulates NSCLC cell radio-sensitivity through directly inhibiting BTG2 expression. Biochemical and biophysical research communications 34 25576360
2023 Btg2 Promotes Focal Segmental Glomerulosclerosis via Smad3-Dependent Podocyte-Mesenchymal Transition. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 32 37749872
2015 MicroRNA‑21 regulates the expression of BTG2 in HepG2 liver cancer cells. Molecular medicine reports 32 26151427
2015 BTG2 inhibits the proliferation and metastasis of osteosarcoma cells by suppressing the PI3K/AKT pathway. International journal of clinical and experimental pathology 30 26722427
2018 MicroRNA-652 induces NED in LNCaP and EMT in PC3 prostate cancer cells. Oncotarget 29 29721191
2008 Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction. Journal of bioenergetics and biomembranes 29 18679777
2018 miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane permeabilization (MOMP) through PUMA/BBC3 and BTG2. Cell death & disease 28 29352138
2015 Galectin-3 Overrides PTRF/Cavin-1 Reduction of PC3 Prostate Cancer Cell Migration. PloS one 28 25942420
2008 Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21. Journal of neurochemistry 28 18194438
2012 B-cell translocation gene 2 (BTG2) stimulates cellular antioxidant defenses through the antioxidant transcription factor NFE2L2 in human mammary epithelial cells. The Journal of biological chemistry 27 22493435
2014 Inhibition of bladder cancer invasion by Sp1-mediated BTG2 expression via inhibition of DNA methyltransferase 1. The FEBS journal 26 25284287
2009 TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest. Cellular signalling 26 19263516
2021 Elevation of miR-146a Inhibits BTG2/BAX Expression to Ameliorate Postoperative Cognitive Dysfunction Following Probiotics (VSL#3) Treatment. Molecular neurobiology 25 33725320
2018 Estradiol Prevents High Glucose-Induced β-cell Apoptosis by Decreased BTG2 Expression. Scientific reports 25 30115961
1995 Expression of activin and activin receptors in pc3 human prostatic-cancer cells. International journal of oncology 25 21556577
2021 Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion. Journal of neuroinflammation 24 33812385
2020 p53/PGC‑1α‑mediated mitochondrial dysfunction promotes PC3 prostate cancer cell apoptosis. Molecular medicine reports 24 32377739
2016 Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3. International journal of molecular sciences 24 27187384
2015 Antitumoral and Antioxidant Potential of Egyptian Propolis Against the PC3 Prostate Cancer Cell Line. Asian Pacific journal of cancer prevention : APJCP 24 26625775
2016 Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA. Scientific reports 23 27346836
2015 Control of the Normal and Pathological Development of Neural Stem and Progenitor Cells by the PC3/Tis21/Btg2 and Btg1 Genes. Journal of cellular physiology 23 25967096
2008 TIS21/(BTG2) negatively regulates estradiol-stimulated expansion of hematopoietic stem cells by derepressing Akt phosphorylation and inhibiting mTOR signal transduction. Stem cells (Dayton, Ohio) 23 18556508
2005 The BTG/TOB family protein TIS21 regulates stage-specific proliferation of developing thymocytes. European journal of immunology 23 16163674
2021 Exosomal microRNA-15a from ACHN cells aggravates clear cell renal cell carcinoma via the BTG2/PI3K/AKT axis. The Kaohsiung journal of medical sciences 22 34337864
2017 BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma. Digestive diseases and sciences 22 29098552
2015 Intracellular EP2 prostanoid receptor promotes cancer-related phenotypes in PC3 cells. Cellular and molecular life sciences : CMLS 22 25828575
1995 The role of prohormone convertases PC1 (PC3) and PC2 in the cell-specific processing of proglucagon. Biochemical and biophysical research communications 22 7864855
2022 DSCR9/miR-21-5p axis inhibits pancreatic cancer proliferation and resistance to gemcitabine via BTG2 signaling. Acta biochimica et biophysica Sinica 21 36789695
2020 LINC01089 inhibits the progression of cervical cancer via inhibiting miR-27a-3p and increasing BTG2. The journal of gene medicine 21 33025678
2014 Tis21 is required for adult neurogenesis in the subventricular zone and for olfactory behavior regulating cyclins, BMP4, Hes1/5 and Ids. Frontiers in cellular neuroscience 21 24744701
2008 Expression of nucleostemin in prostate cancer and its effect on the proliferation of PC-3 cells. Chinese medical journal 21 18304460
2021 Pro-angiogenic effect of PC-3 exosomes in endothelial cells in vitro. Cellular signalling 20 34474113
1998 Overexpression of the PC3/TIS21/BTG2 mRNA is part of the stress response induced by acute pancreatitis in rats. Biochemical and biophysical research communications 20 9712737
1994 Expression of PC2 and PC1/PC3 in human pheochromocytomas. Molecular and cellular endocrinology 20 8206338
2016 Enhanced Cytotoxicity of Biomolecules Loaded Metallic Silver Nanoparticles Against Human Liver (HepG2) and Prostate (PC3) Cancer Cell Lines. Journal of nanoscience and nanotechnology 19 27483851
2023 miR-21-5p prevents doxorubicin-induced cardiomyopathy by downregulating BTG2. Heliyon 18 37131441
2021 Circular RNA circ_0014717 Suppresses Hepatocellular Carcinoma Tumorigenesis Through Regulating miR-668-3p/BTG2 Axis. Frontiers in oncology 18 33598424
2019 Extracellular Electrophysiology in the Prostate Cancer Cell Model PC-3. Sensors (Basel, Switzerland) 18 30609788
2019 lncRNA SNHG5 Modulates Endometrial Cancer Progression via the miR-25-3p/BTG2 Axis. Journal of oncology 18 31885582
2006 Inhibition of caveolin-1 expression by incadronate in PC-3 prostate cells. Anticancer research 18 16886623
2015 Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells. Asian Pacific journal of cancer prevention : APJCP 17 26028116
2013 BTG2 overexpression increases the radiosensitivity of breast cancer cells in vitro and in vivo. Oncology research 17 24308156
2017 Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2. Frontiers in cellular neuroscience 16 28740463
2006 Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells. Journal of receptor and signal transduction research 16 16777715
2002 Genes modulated by expression of GD3 synthase in Chinese hamster ovary cells. Evidence that the Tis21 gene is involved in the induction of GD3 9-O-acetylation. The Journal of biological chemistry 16 12493756
2025 Predicting the molecular mechanism of ginger targeting PRMT1/BTG2 axis to inhibit gastric cancer based on WGCNA and machine algorithms. Phytomedicine : international journal of phytotherapy and phytopharmacology 15 40446574
2021 Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2-YY1 signaling pathway. Scientific reports 15 34556771
2010 BTG2 is an LXXLL-dependent co-repressor for androgen receptor transcriptional activity. Biochemical and biophysical research communications 15 21172304
2022 Saffron extract feed improves the antioxidant status of laying hens and the inhibitory effect on cancer cells (PC3 and MCF7) Growth. Veterinary medicine and science 14 36063535
2016 Shifting p53-induced senescence to cell death by TIS21(/BTG2/Pc3) gene through posttranslational modification of p53 protein. Cellular signalling 14 27208501
2022 LncRNA CARMN inhibits cervical cancer cell growth via the miR-92a-3p/BTG2/Wnt/β-catenin axis. Physiological genomics 13 36314369
2020 MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells. OncoTargets and therapy 13 32764979
2013 TIS21(/BTG2/PC3) inhibits interleukin-6 expression via downregulation of STAT3 pathway. Cellular signalling 13 23917204
2022 BTG2 suppresses renal cell carcinoma progression through N6-methyladenosine. Frontiers in oncology 12 36591524