Affinage

TOB1

Protein Tob1 · UniProt P50616

Length
345 aa
Mass
38.2 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOB1 is an anti-proliferative scaffold protein that restrains cell growth through two interconnected mechanisms: transcriptional repression via Smad-dependent signaling and promotion of mRNA deadenylation via the CCR4-NOT complex. In the nucleus, TOB1 associates with receptor-regulated Smads (Smad1/5/8) to suppress BMP signaling and with Smad2/4 to repress IL-2 transcription, and it recruits HDAC to silence the cyclin D1 promoter, with tob-deficient mice exhibiting increased bone mass and predisposition to spontaneous tumors (PMID:11163184, PMID:11694881, PMID:12756225). In the cytoplasm, its N-terminal BTG domain binds the CAF1 (CNOT7/CNOT8) deadenylase subunit while two C-terminal PAM2 motifs engage PABPC1, bridging the CCR4-NOT complex to polyadenylated mRNAs and accelerating their decay—an activity essential for its anti-proliferative function (PMID:17785442, PMID:19276069, PMID:23236473). TOB1 anti-proliferative activity is negatively regulated by ERK1/2-mediated phosphorylation at Ser152/154/164 and by SCF-Skp2- and Cul4-DDB1(Cdt2)-dependent ubiquitin-proteasomal degradation, while Cdc7-mediated phosphorylation stabilizes TOB1 to promote cell survival after DNA damage (PMID:12050114, PMID:16951159, PMID:23066029).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Identification of TOB1 as an anti-proliferative protein that physically interacts with ErbB2 established the gene's foundational role as a growth suppressor regulated by receptor tyrosine kinase signaling.

    Evidence GST pulldown and co-immunoprecipitation with ErbB2, cell growth suppression assay in NIH3T3 cells

    PMID:8632892

    Open questions at the time
    • Mechanism of anti-proliferative action unknown
    • Downstream targets not identified
    • Whether ErbB2 interaction is direct or indirect in vivo unclear
  2. 1999 Medium

    Discovery that TOB1 binds hCaf1, a deadenylase/transcription factor complex component, opened a second mechanistic axis beyond receptor tyrosine kinase interaction.

    Evidence Co-immunoprecipitation of Tob N-terminal domain with hCaf1

    PMID:10602502

    Open questions at the time
    • Functional consequence of Caf1 interaction not demonstrated
    • No structural detail of binding interface
    • Role of Caf1 enzymatic activity in Tob function unknown
  3. 2000 High

    Demonstration that TOB1 associates with BMP-responsive Smads and that tob-knockout mice have increased bone mass established TOB1 as a physiological negative regulator of BMP/Smad signaling in bone.

    Evidence Co-immunoprecipitation with Smad1/5/8, tob−/− knockout mouse bone phenotype, BMP2-responsive reporter assay

    PMID:11163184

    Open questions at the time
    • Whether Tob acts as a direct transcriptional corepressor at BMP-target promoters not shown
    • Mechanism of Smad-dependent repression unclear
    • Relationship between BMP suppression and anti-proliferative activity not delineated
  4. 2001 High

    Finding that TOB1 cooperates with Smad2/4 to repress IL-2 transcription in anergic T cells extended the Smad-dependent mechanism to adaptive immunity and identified a specific target gene.

    Evidence Co-immunoprecipitation with Smad2/4, EMSA at IL-2 promoter, antisense knockdown in anergic T cells

    PMID:11694881

    Open questions at the time
    • Direct binding of Tob to the IL-2 promoter DNA not demonstrated
    • Post-transcriptional regulation of IL-2 not addressed
    • Role beyond T cell anergy not examined
  5. 2002 High

    Identification of ERK1/2-mediated phosphorylation at Ser152/154/164 as an inactivation mechanism resolved how mitogenic signaling overrides TOB1's growth-suppressive function, placing TOB1 in the ERK–cyclin D1–Rb pathway.

    Evidence In vitro kinase assays, Ser-to-Ala/Glu mutagenesis, tob−/− MEFs, cell cycle analysis; independently confirmed by two labs

    PMID:12050114 PMID:12151396

    Open questions at the time
    • Whether phosphorylation disrupts specific protein interactions not determined
    • In vivo phosphorylation dynamics during cell cycle not tracked
    • Contribution of JNK2 phosphorylation versus ERK phosphorylation not resolved
  6. 2003 High

    Discovery that TOB1 recruits HDAC to repress the cyclin D1 promoter and that tob−/− mice develop spontaneous tumors established TOB1 as a bona fide tumor suppressor acting through chromatin modification.

    Evidence Tob−/− mouse tumor formation, cyclin D1 reporter assay, co-immunoprecipitation with HDAC

    PMID:12756225

    Open questions at the time
    • Identity of specific HDAC isoform(s) not resolved
    • Whether HDAC recruitment is direct or Smad-mediated unknown
    • Tumor spectrum and penetrance not fully characterized
  7. 2003 High

    Identification of TOB1 interaction with inhibitory Smads 6/7, enhancing their association with BMP type I receptors, revealed a second mode of BMP pathway suppression at the receptor level.

    Evidence Yeast two-hybrid, co-immunoprecipitation, Xenopus embryo functional assay

    PMID:12782279

    Open questions at the time
    • Relative contribution of R-Smad versus I-Smad mechanisms not quantified
    • Stoichiometry of Tob–Smad6 complex at the receptor unknown
  8. 2004 High

    Mapping of a bipartite NLS and CRM1-dependent NES demonstrated that TOB1's anti-proliferative function requires nuclear localization and that ErbB2-driven oncogenesis antagonizes this by promoting nuclear export.

    Evidence GFP-Tob localization with NLS/NES mutagenesis, leptomycin B treatment, cell cycle assays across two independent studies

    PMID:15051490 PMID:15235587

    Open questions at the time
    • Signaling pathway from ErbB2 to NES activation not defined
    • Whether cytoplasmic Tob retains deadenylation function not tested
  9. 2006 High

    Identification of SCF-Skp2 as the E3 ligase targeting TOB1 for proteasomal degradation explained how TOB1 protein levels are controlled during cell cycle progression.

    Evidence In vitro ubiquitination reconstitution, Skp2−/− fibroblasts showing TOB1 stabilization, Skp2 knockdown

    PMID:16951159

    Open questions at the time
    • Phosphodegron on Tob recognized by Skp2 not mapped
    • Interplay between Skp2 and Cul4-DDB1 pathways not clarified
  10. 2007 High

    Demonstration that TOB1 simultaneously bridges PABPC1 and the CAF1-CCR4 deadenylase to enhance mRNA deadenylation in vivo unified the Caf1-binding and PABP-binding activities into a coherent recruitment model for mRNA decay.

    Evidence GST pulldown, co-immunoprecipitation, transcriptional pulse-chase mRNA decay assay, P-body co-localization

    PMID:17785442

    Open questions at the time
    • Specific mRNA targets not identified
    • Whether deadenylation is selective or global not determined
    • Structural basis of simultaneous bridging not resolved
  11. 2009 High

    Crystal structure of the TOB1 N-terminal domain bound to Caf1 revealed the atomic interface and showed that Caf1 complex formation, but not Caf1 deadenylase catalytic activity per se, is essential for growth inhibition.

    Evidence X-ray crystallography of Tob–hCaf1 complex, functional mutagenesis of interface residues

    PMID:19276069

    Open questions at the time
    • Full-length Tob structure (including disordered C-terminus) unavailable
    • Whether Caf1 interaction scaffolds additional effectors beyond deadenylation not tested
  12. 2010 High

    NMR analysis revealing two PAM2 motifs in the disordered C-terminus binding PABPC1, competing with eRF3, provided a thermodynamic model for translation termination-coupled deadenylation mediated by TOB1.

    Evidence NMR spectroscopy, quantitative binding affinity measurements (Kd ~20 μM)

    PMID:20595394

    Open questions at the time
    • Competition with eRF3 not validated in cells
    • Functional consequence of dual PAM2 motifs versus single motif not dissected
  13. 2011 High

    Discovery that TOB1 bridges CPEB3 and Caf1 into a ternary complex for target-specific mRNA deadenylation demonstrated that TOB1 can confer substrate selectivity on the deadenylase machinery.

    Evidence Co-immunoprecipitation, GST pulldown, in vitro deadenylation reconstitution, dominant-negative mutant analysis

    PMID:21336257

    Open questions at the time
    • Full set of RNA-binding protein partners that confer selectivity not cataloged
    • In vivo mRNA targets of CPEB3–Tob pathway not identified genome-wide
  14. 2012 High

    Establishing that ERK phosphorylation of TOB1 does not affect its deadenylation-promoting activity revealed that TOB1 suppresses proliferation through at least two separable mechanisms: deadenylation and a phosphorylation-sensitive pathway.

    Evidence mRNA tethering functional assay, phosphomimetic mutagenesis, cell proliferation assays

    PMID:22252318 PMID:23236473

    Open questions at the time
    • Identity of the phosphorylation-sensitive anti-proliferative mechanism unknown
    • Whether the two mechanisms converge on the same target mRNAs not tested
  15. 2012 High

    Identification of Cul4-DDB1(Cdt2) as a second E3 ligase for TOB1 and Cdc7 as a stabilizing kinase after UV damage revealed a DNA damage-responsive circuit where TOB1 stabilization promotes survival.

    Evidence Ubiquitination and phosphorylation assays, tob−/− MEFs, apoptosis assays after UV irradiation

    PMID:18850001 PMID:23066029

    Open questions at the time
    • Cdt2 degron on Tob not precisely mapped
    • How Cdc7 phosphorylation blocks Cdt2 recognition structurally undefined
    • Relative contribution of Skp2 versus Cdt2 pathway in different contexts unknown
  16. 2013 High

    Demonstration that Tob1 deficiency in CD4+ T cells drives aggressive autoimmune encephalomyelitis and impairs Treg function established TOB1 as a critical checkpoint in T cell-mediated autoimmunity.

    Evidence Tob1−/− mice in EAE model, adoptive transfer of Tob1−/− CD4+ T cells into Rag1−/− recipients

    PMID:23797093

    Open questions at the time
    • Molecular targets in Tregs responsible for functional impairment not identified
    • Whether deadenylation or Smad pathway underlies T cell phenotype unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the genome-wide identity of mRNAs selectively targeted by TOB1-mediated deadenylation, the structural basis for full-length TOB1 function, the relative contributions of transcriptional repression versus mRNA decay in each biological context, and the mechanism by which ERK phosphorylation impairs anti-proliferative activity independently of deadenylation.
  • No genome-wide CLIP or similar unbiased identification of TOB1 mRNA targets
  • No full-length TOB1 structure
  • Phosphorylation-sensitive anti-proliferative mechanism molecularly undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1266738 Developmental Biology 2
Partners
CNOT7CNOT8CPEB3ERBB2PABPC1SKP2SMAD1SMAD4
Complex memberships
CCR4-NOT

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TOB1 (Tob) was identified as a protein that physically interacts with the receptor tyrosine kinase p185erbB2 (ErbB2) via its C-terminal half, and this interaction antagonizes Tob's anti-proliferative activity; the interaction was confirmed by co-immunoprecipitation and GST pulldown. GST pulldown, co-immunoprecipitation, cell growth suppression assay Oncogene High 8632892
2000 Tob associates with receptor-regulated Smads (Smad1, Smad5, Smad8) and colocalizes with them in nuclear bodies upon BMP2 stimulation; tob-deficient mice show increased bone mass and elevated BMP2-induced bone formation, and Tob overexpression represses BMP2-induced Smad-mediated transcriptional activation. Co-immunoprecipitation, immunolocalization, tob knockout mouse, transcriptional reporter assay Cell High 11163184
2001 In anergic T cells, Tob associates with Smad2 and Smad4 and enhances Smad DNA-binding at the −105 negative regulatory element of the IL-2 promoter, thereby suppressing IL-2 transcription independently of NFAT, AP-1, or NF-κB. Co-immunoprecipitation, EMSA/DNA-binding assay, antisense oligonucleotide knockdown, transcriptional reporter assay Nature immunology High 11694881
1999 The N-terminal half of Tob associates with hCaf1 (a component of the CCR4 transcription factor/deadenylase complex), and Caf1 associates with cyclin-dependent kinases; this interaction was shown for both Tob and Tob2. Co-immunoprecipitation, protein interaction assay Oncogene Medium 10602502
2002 Tob is phosphorylated at Ser152, Ser154, and Ser164 by Erk1 and Erk2 upon growth-factor stimulation; phosphorylation abolishes Tob's anti-proliferative function and suppression of cyclin D1 expression, placing Tob downstream of Erk and upstream of Rb in the G1 progression pathway. In vitro kinase assay, site-directed mutagenesis (Ser→Ala/Glu), tob−/− MEFs, cell cycle analysis Genes & development High 12050114
2002 ERK2 and JNK2 bind to and phosphorylate Tob in vitro; an ERK docking site resides in the N-terminal portion of Tob and phosphorylation sites in the C-terminal region; phosphomimetic Tob mutants show reduced anti-proliferative activity. Two-hybrid screen, in vitro kinase assay, cell cycle analysis The Journal of biological chemistry High 12151396
2001 p90rsk1 associates with Tob in vitro and in vivo and phosphorylates Tob at least in vitro, suggesting that Tob function is regulated downstream of receptor tyrosine kinases via p90rsk1-mediated phosphorylation. In vitro kinase assay, co-immunoprecipitation Genes to cells Medium 11260258
2003 Tob acts as a transcriptional corepressor of the cyclin D1 promoter through interaction with histone deacetylase; tob−/− mice are predisposed to spontaneous tumor formation, and cyclin D1 mRNA is increased in tob−/− cells. tob−/− mouse tumor model, transcriptional reporter assay, co-immunoprecipitation with HDAC Genes & development High 12756225
2003 Tob interacts with inhibitory Smads 6 and 7 (identified by yeast two-hybrid), colocalizes with Smad6 at the plasma membrane, and enhances Smad6 interaction with activated BMP type I receptors, thereby cooperating with inhibitory Smads to suppress BMP signaling. Yeast two-hybrid, co-immunoprecipitation, immunolocalization, Xenopus embryo assay Mechanisms of development High 12782279
2004 Tob is a nuclear protein imported via a bipartite NLS (residues 18–40) and exported via an NES (residues 2–14); in oncogenic ErbB2-transformed cells nuclear export is facilitated, reducing anti-proliferative activity; mutation of the NLS impairs anti-proliferative function. GFP-tagged Tob localization, leptomycin B treatment, NLS/NES mutagenesis, cell cycle assay Oncogene / Experimental cell research High 15051490 15235587
2005 Tob interacts with poly(A)-binding protein (PABP) and inducible PABP (iPABP) via their C-terminal regions; Tob abrogates iPABP-enhanced translation of IL-2 mRNA in vitro, implicating Tob in translational suppression of IL-2 mRNA in anergic T cells. Expression library screen with GST-Tob, co-immunoprecipitation, GST pulldown, in vitro translation assay Genes to cells High 15676026
2006 Tob1 is degraded via the ubiquitin-proteasome pathway through the SCF-Skp2 ubiquitin ligase complex; Skp2 interacts with Tob1 and facilitates its ubiquitination in vitro and in intact cells; Tob1 is stabilized in Skp2−/− fibroblasts. Co-immunoprecipitation, in vitro ubiquitination assay, Skp2 KO fibroblasts, Skp2 knockdown Cancer research High 16951159
2002 Tob and other BTG/Tob family members (BTG1, BTG2, Tob2) are degraded by the ubiquitin-proteasome system; the C-terminal regions are necessary and sufficient to confer instability, as demonstrated by proteasome inhibitor treatment and multiubiquitination assays. Proteasome inhibitor treatment, ubiquitin co-expression/immunoprecipitation, C-terminal truncation/fusion constructs European journal of biochemistry Medium 12135500
2007 Human TOB simultaneously interacts with the CCR4-CAF1 deadenylase complex and cytoplasmic PABPC1; this bridging interaction is required for TOB to enhance mRNA deadenylation in vivo; TOB colocalizes with P-bodies by immunofluorescence. GST pulldown, co-immunoprecipitation, mutagenesis, transcriptional pulsing mRNA decay assay, immunofluorescence Molecular and cellular biology High 17785442
2008 Tob associates with the CCR4-NOT complex; the C-terminal half of Tob interacts with Cnot1 (core CCR4-NOT subunit) and the deadenylase activity of the complex is suppressed in vitro by Tob. Proteomics/co-immunoprecipitation, in vitro deadenylase activity assay Cancer science Medium 18377426
2009 Crystal structure of the Tob N-terminal domain in complex with human Caf1 (hCaf1) revealed that Tob exhibits a novel fold and that both Box A and Box B of Tob mediate hCaf1 association; deadenylase activity of Caf1 is not required but complex formation with Caf1 is essential for cell growth inhibition. X-ray crystallography, cell growth assay with wild-type and mutant proteins The Journal of biological chemistry High 19276069
2010 NMR and biochemical analyses showed that Tob consists of a structured N-terminal BTG-Tob domain (binds Caf1) and an unstructured C-terminal region containing two PAM2 motifs (bind PABPC1 C-terminal PABC domain, Kd ~20 μM); competition between Tob and eRF3 for PABPC1 provides a thermodynamic mechanism for translation termination-coupled deadenylation. NMR spectroscopy, Western blot quantification, binding affinity measurement The Journal of biological chemistry High 20595394
2011 Tob binds directly to CPEB3 via Tob's C-terminal unstructured region; Tob then recruits Caf1 deadenylase to form a ternary Tob-CPEB3-Caf1 complex, mediating CPEB3-accelerated mRNA deadenylation; dominant-negative Caf1 or Tob mutants abrogate this deadenylation. Co-immunoprecipitation, GST pulldown, in vitro deadenylation assay, dominant-negative mutant analysis The EMBO journal High 21336257
2012 The anti-proliferative activity of TOB1 (and BTG2) requires interaction with Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits; mutations abolishing this interaction eliminate anti-proliferative activity and effects on mRNA abundance and translation without requiring other CCR4-NOT subunits. Structure-guided mutagenesis, cell proliferation assay, siRNA knockdown of CCR4-NOT subunits, mRNA abundance and translation measurement PloS one High 23236473
2012 TOB1 and TOB2 promote deadenylation by recruiting CAF1-CCR4 complex to mRNA 3' ends via simultaneous binding of CAF1 and PABP (recruitment model); TOBs' deadenylation-promoting and anti-proliferative activities are linked; phosphorylation of the three Erk sites does not affect deadenylation, indicating at least two independent mechanisms for cell growth arrest. mRNA tethering functional assay, biochemical analyses, mutagenesis Molecular and cellular biology High 22252318
2010 Tob1 directly associates with Caf1 and with cyclin-dependent kinase 1 (Cdk1) and modulates Cdk1 kinase activity; Tob1 deletion increases hepatocyte proliferation and accelerates liver regeneration; Tob1 protein decreases after hepatectomy via post-transcriptional mechanisms. Co-immunoprecipitation, kinase activity assay, Tob1 KO mouse hepatectomy model The Journal of experimental medicine High 20513747
2012 UV irradiation promotes proteasome-dependent degradation of Tob; degradation-resistant Tob impairs UV-induced apoptosis while siRNA knockdown of Tob induces apoptosis independently of p53; Cul4-DDB1(Cdt2) mediates Tob ubiquitination, and Cdc7 phosphorylates Tob to inhibit this degradation, providing a pro-survival pathway after mild DNA damage. siRNA knockdown, Cul4/Cdc7 interaction and phosphorylation assays, tob−/− mice/MEFs, apoptosis assays Oncogene / The Journal of biological chemistry High 18850001 23066029
2001 PMA-induced phosphorylation of MARCKS increases MARCKS binding to Tob, displacing Tob from ErbB2 and leading to ErbB2 activation; the phosphorylation site domain (PSD) of MARCKS mediates its interaction with Tob. Co-immunoprecipitation, phorbol ester treatment, ErbB2 phosphorylation assay Biochemical and biophysical research communications Medium 11327693
2005 Tob1 and Tob2 proteins suppress steroid hormone receptor-dependent transcriptional activation in osteoblastic cells; Tob1 inhibits nuclear foci formation of dihydrotestosterone-bound androgen receptor as visualized by GFP-tagged AR live imaging. Luciferase reporter assay, confocal live imaging of GFP-AR, mutagenesis of LXXLL motif Molecular and cellular endocrinology Medium 15664454
2015 Tob1 and Tob2 inhibit proliferation of mouse embryonic stem cells by promoting degradation of Id3 mRNA; Tob1/Tob2 double-knockout ESCs grow faster without loss of pluripotency, and Id3 mRNA is a directly targeted transcript of the BMP4 signaling pathway. Tob1/2 knockout ESC lines, mRNA stability assay, cell proliferation assay Biochemical and biophysical research communications Medium 25951976
2008 TOB1 acts as a transcriptional co-activator of the Dpp2 promoter in concert with KLF2, linking two quiescence-maintenance factors to Dpp2 transcription in lymphocytes. Promoter-reporter (luciferase) assay Molecular immunology Low 18555530
2014 Arsenite-induced oxidative stress inhibits mRNA deadenylation primarily through proteolytic degradation of Tob and Pan3; siRNA knockdown of Tob and Pan3 recapitulates mRNA poly(A) tail stabilization, independent of eIF2α kinase HRI. siRNA knockdown, poly(A) tail length assay, Western blot Biochemical and biophysical research communications Medium 25446091
2013 Tob1 deficiency in CD4+ T cells is sufficient to drive aggressive experimental autoimmune encephalomyelitis (EAE); Tob1−/− Treg cells showed reduced regulatory function; reconstitution of Rag1−/− mice with Tob1−/− CD4+ T cells recapitulated the aggressive EAE phenotype. Tob1 KO mouse EAE model, T cell transfer into Rag1−/− mice, T cell phenotyping The Journal of experimental medicine High 23797093
2021 TOB1 associates with Smad4/5 to induce ID2 expression, which in turn restrains Th1/Th17 cell differentiation; Tob1−/− mice develop severe colitis, and Rag1−/− mice reconstituted with Tob1−/− T cells also develop severe colitis. Co-immunoprecipitation (Smad4/5), lentiviral overexpression/knockdown, RNA-seq, T cell transfer colitis model Cellular and molecular gastroenterology and hepatology Medium 34920145
1997 Mouse Tob was cloned and shown to be ubiquitously expressed; like human Tob, mouse Tob contains proline/glutamine-rich sequences characteristic of transcription factors and has an ATTTA motif in the 3'-UTR typical of immediate-early genes, consistent with a role in response to extracellular signals. Molecular cloning, Northern blot, sequence analysis Gene Low 9210596
2015 Tob1 protein is localized to P-bodies (co-immunoprecipitation and co-localization with Dcp2) in round spermatids and oocytes, consistent with a post-transcriptional regulatory role in germ cells. Immunofluorescence, co-immunoprecipitation with Dcp2, RT-ddPCR expression profiling Cell and tissue research Low 26662055

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 262 11163184
2010 The mammalian anti-proliferative BTG/Tob protein family. Journal of cellular physiology 245 19746446
2001 Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nature immunology 223 11694881
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
1996 Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity. Oncogene 179 8632892
2007 Human TOB, an antiproliferative transcription factor, is a poly(A)-binding protein-dependent positive regulator of cytoplasmic mRNA deadenylation. Molecular and cellular biology 138 17785442
1999 Tob2, a novel anti-proliferative Tob/BTG1 family member, associates with a component of the CCR4 transcriptional regulatory complex capable of binding cyclin-dependent kinases. Oncogene 129 10602502
2002 Phosphorylation of three regulatory serines of Tob by Erk1 and Erk2 is required for Ras-mediated cell proliferation and transformation. Genes & development 119 12050114
2012 The C-terminal domain of Fcj1 is required for formation of crista junctions and interacts with the TOB/SAM complex in mitochondria. Molecular biology of the cell 101 22496419
2003 Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes & development 100 12756225
1998 ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system. Oncogene 97 9632145
2009 Structural basis for the antiproliferative activity of the Tob-hCaf1 complex. The Journal of biological chemistry 90 19276069
2010 Mdm10 as a dynamic constituent of the TOB/SAM complex directs coordinated assembly of Tom40. EMBO reports 84 20111053
2009 BTG/TOB factors impact deadenylases. Trends in biochemical sciences 82 19828319
2006 Differential mechanisms of microparticle transfer toB cells and monocytes: anti-inflammatory propertiesof microparticles. European journal of immunology 81 16479543
2002 Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects. Genes to cells : devoted to molecular & cellular mechanisms 72 11856371
2020 Exosomal miRNA-486-5p derived from rheumatoid arthritis fibroblast-like synoviocytes induces osteoblast differentiation through the Tob1/BMP/Smad pathway. Biomaterials science 71 32406432
2011 Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase. The EMBO journal 69 21336257
2005 Interaction of anti-proliferative protein Tob with poly(A)-binding protein and inducible poly(A)-binding protein: implication of Tob in translational control. Genes to cells : devoted to molecular & cellular mechanisms 64 15676026
2000 Cloning of PC3B, a novel member of the PC3/BTG/TOB family of growth inhibitory genes, highly expressed in the olfactory epithelium. Genomics 64 10995567
2012 The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex. PloS one 63 23236473
2004 Assembly of the TOB complex of mitochondria. The Journal of biological chemistry 62 15590639
2002 Identification of the Anti-proliferative protein Tob as a MAPK substrate. The Journal of biological chemistry 61 12151396
2000 A novel member of the tob family of proteins controls sexual fate in Caenorhabditis elegans germ cells. Developmental biology 61 10625537
2006 Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer research 52 16951159
2012 Tob1 induces apoptosis and inhibits proliferation, migration and invasion of gastric cancer cells by activating Smad4 and inhibiting β‑catenin signaling. International journal of oncology 51 22710759
2002 Altered expression of a cell-cycle suppressor gene, Tob-1, in endometriotic cells by cDNA array analyses. Fertility and sterility 51 12372467
2017 Three TOB1-related YABBY genes are required to maintain proper function of the spikelet and branch meristems in rice. The New phytologist 50 28556940
2004 Nuclear localization of Tob is important for regulation of its antiproliferative activity. Oncogene 50 15235587
2003 Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer. Cancer letters 48 14643028
2002 Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system. European journal of biochemistry 48 12135500
2007 Tob genes in development and homeostasis. Developmental dynamics : an official publication of the American Association of Anatomists 47 17304515
2012 Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activities. Molecular and cellular biology 43 22252318
2003 Tob proteins enhance inhibitory Smad-receptor interactions to repress BMP signaling. Mechanisms of development 43 12782279
2013 Tob1 plays a critical role in the activation of encephalitogenic T cells in CNS autoimmunity. The Journal of experimental medicine 40 23797093
2001 Association of ANA, a member of the antiproliferative Tob family proteins, with a Caf1 component of the CCR4 transcriptional regulatory complex. Japanese journal of cancer research : Gann 39 11429045
2013 IL-4-induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells. European journal of immunology 38 24307243
2005 Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid. Cancer letters 37 15766599
2011 Suppression of human lung cancer cell proliferation and metastasis in vitro by the transducer of ErbB-2.1 (TOB1). Acta pharmacologica Sinica 36 22158108
2009 TOB suppresses breast cancer tumorigenesis. International journal of cancer 36 19569230
2004 Tob deficiency superenhances osteoblastic activity after ovariectomy to block estrogen deficiency-induced osteoporosis. Proceedings of the National Academy of Sciences of the United States of America 35 15100414
2020 LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis. Biochemical and biophysical research communications 32 32307083
2008 Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex. Cancer science 32 18377426
2019 MiR-32-5p Regulates Radiosensitization, Migration And Invasion Of Colorectal Cancer Cells By Targeting TOB1 Gene. OncoTargets and therapy 31 31814731
2012 Chloroplast β-barrel proteins are assembled into the mitochondrial outer membrane in a process that depends on the TOM and TOB complexes. The Journal of biological chemistry 29 22745120
2017 MicroRNA-590 promotes pathogenic Th17 cell differentiation through targeting Tob1 and is associated with multiple sclerosis. Biochemical and biophysical research communications 28 28947212
2016 TOB1 Deficiency Enhances the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Tendon-Bone Healing in a Rat Rotator Cuff Repair Model. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 26824451
2001 Tob-mediated cross-talk between MARCKS phosphorylation and ErbB-2 activation. Biochemical and biophysical research communications 28 11327693
2018 MicroRNA-371a-3p promotes progression of gastric cancer by targeting TOB1. Cancer letters 27 30529155
2005 The negative cell cycle regulator, Tob (transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory. Neuroscience 27 15730870
2015 Transducer of ERBB2.1 (TOB1) as a Tumor Suppressor: A Mechanistic Perspective. International journal of molecular sciences 26 26694352
2010 Tob1 is a constitutively expressed repressor of liver regeneration. The Journal of experimental medicine 25 20513747
2006 The negative cell cycle regulator, Tob (transducer of ErbB-2), is involved in motor skill learning. Biochemical and biophysical research communications 25 16414345
2015 Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation. Oncogene 24 26165839
2009 Tob, a member of the APRO family, regulates immunological quiescence and tumor suppression. Cell cycle (Georgetown, Tex.) 24 19270514
2019 TOB1-AS1 suppresses non-small cell lung cancer cell migration and invasion through a ceRNA network. Experimental and therapeutic medicine 23 31772627
2018 Long noncoding RNA TOB1-AS1, an epigenetically silenced gene, functioned as a novel tumor suppressor by sponging miR-27b in cervical cancer. American journal of cancer research 23 30210918
2011 Identification of novel subregions of LOH in gastric cancer and analysis of the HIC1 and TOB1 tumor suppressor genes in these subregions. Molecules and cells 23 21533545
2010 Quantitative characterization of Tob interactions provides the thermodynamic basis for translation termination-coupled deadenylase regulation. The Journal of biological chemistry 23 20595394
2005 The BTG/TOB family protein TIS21 regulates stage-specific proliferation of developing thymocytes. European journal of immunology 23 16163674
1997 Sequence and developmental expression of AmphiTob, an amphioxus homolog of vertebrate Tob in the PC3/BTG1/Tob family of tumor suppressor genes. Developmental dynamics : an official publication of the American Association of Anatomists 23 9286591
2020 LncRNA NR2F1-AS1 Regulates miR-371a-3p/TOB1 Axis to Suppress Proliferation of Colorectal Cancer Cells. Cancer biotherapy & radiopharmaceuticals 21 32407174
2011 Phosphorylation state of a Tob/BTG protein, FOG-3, regulates initiation and maintenance of the Caenorhabditis elegans sperm fate program. Proceedings of the National Academy of Sciences of the United States of America 21 21571637
2021 TOB1 Blocks Intestinal Mucosal Inflammation Through Inducing ID2-Mediated Suppression of Th1/Th17 Cell Immune Responses in IBD. Cellular and molecular gastroenterology and hepatology 20 34920145
2013 Enhanced radiosensitivity of NSCLC cells by transducer of erbB2.1 (TOB1) through modulation of the MAPK/ERK pathway. Oncology reports 20 23589165
2011 The Neurospora crassa TOB complex: analysis of the topology and function of Tob38 and Tob37. PloS one 20 21980517
2005 Tob proteins suppress steroid hormone receptor-mediated transcriptional activation. Molecular and cellular endocrinology 20 15664454
2017 Decreased TOB1 expression and increased phosphorylation of nuclear TOB1 promotes gastric cancer. Oncotarget 19 29088861
2015 BTG/Tob family members Tob1 and Tob2 inhibit proliferation of mouse embryonic stem cells via Id3 mRNA degradation. Biochemical and biophysical research communications 19 25951976
2007 Adenovirus-mediated expression of Tob1 sensitizes breast cancer cells to ionizing radiation. Acta pharmacologica Sinica 19 17883950
2005 Expression of sarcotoxin IA gene via a root-specific tob promoter enhanced host resistance against parasitic weeds in tomato plants. Plant cell reports 19 16217684
1997 Cloning and characterization of the mouse tob gene. Gene 19 9210596
2005 Repression of anti-proliferative factor Tob1 in osteoarthritic cartilage. Arthritis research & therapy 18 15743474
2004 Regulation of subcellular localization of the antiproliferative protein Tob by its nuclear export signal and bipartite nuclear localization signal sequences. Experimental cell research 18 15051490
2001 A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob. Genes to cells : devoted to molecular & cellular mechanisms 18 11260258
2022 Exosomal miR-552-5p promotes tumorigenesis and disease progression via the PTEN/TOB1 axis in gastric cancer. Journal of Cancer 17 35154457
2014 The role of antiproliferative gene Tob1 in the immune system. Clinical & experimental neuroimmunology 17 25071870
2006 Tob is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes. The British journal of dermatology 17 16445768
2002 cAMP and in vivo hypoxia induce tob, ifr1, and fos expression in erythroid cells of the chick embryo. American journal of physiology. Regulatory, integrative and comparative physiology 17 11893628
2012 Inhibition of DNA damage-induced apoptosis through Cdc7-mediated stabilization of Tob. The Journal of biological chemistry 16 23066029
2008 Lymphocyte quiescence factor Dpp2 is transcriptionally activated by KLF2 and TOB1. Molecular immunology 16 18555530
2007 Nitrite metabolism in Debaryomyces hansenii TOB-Y7, a yeast strain involved in tobacco fermentation. Applied microbiology and biotechnology 16 17318539
2021 Expression of TOB/BTG family members in patients with inflammatory bowel disease. Scandinavian journal of immunology 15 33247598
2019 Long non-coding RNA TOB1-AS1 modulates cell proliferation, apoptosis, migration and invasion through miR-23a/NEU1 axis via Wnt/b-catenin pathway in gastric cancer. European review for medical and pharmacological sciences 15 31799657
2007 Twisted gastrulation (Tsg) is regulated by Tob and enhances TGF-beta signaling in activated T lymphocytes. Blood 15 17164348
2002 Enhancing effect of Tob deficiency on bone formation is specific to bone morphogenetic protein-induced osteogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 15 12054157
2021 Identification of miR‑25‑3p as a tumor biomarker: Regulation of cellular functions via TOB1 in breast cancer. Molecular medicine reports 14 33786619
2019 The discovery of shorter synthetic proteolytic peptides derived from Tob1 protein. Peptides 13 30930080
2015 Tob1 enhances radiosensitivity of breast cancer cells involving the JNK and p38 pathways. Cell biology international 12 26377349
2014 Nfatc2 and Tob1 have non-overlapping function in T cell negative regulation and tumorigenesis. PloS one 12 24945807
2008 Proteasome-mediated degradation of Tob is pivotal for triggering UV-induced apoptosis. Oncogene 12 18850001
2012 C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context. Oncogene 11 22797076
2008 Tumor growth suppression by adenovirus-mediated introduction of a cell-growth-suppressing gene tob in a pancreatic cancer model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 18657378
2014 Arsenite inhibits mRNA deadenylation through proteolytic degradation of Tob and Pan3. Biochemical and biophysical research communications 10 25446091
2013 Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway. Oncology reports 10 23756562
2022 Involvement of TOB1 on autophagy in gastric cancer AGS cells via decreasing the activation of AKT/mTOR signaling pathway. PeerJ 9 35186488
2022 The Overexpression of TOB1 Induces Autophagy in Gastric Cancer Cells by Secreting Exosomes. Disease markers 9 35465266
2019 TOB1 suppresses proliferation in K-Ras wild-type pancreatic cancer. Cancer medicine 9 31891232
2015 Tob1 is expressed in developing and adult gonads and is associated with the P-body marker, Dcp2. Cell and tissue research 9 26662055