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Showing TOB1 — TOB is a alias.

TOB1

Protein Tob1 · UniProt P50616

Length
345 aa
Mass
38.2 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TOB1 is an antiproliferative protein that restrains cell growth through two mechanistically distinct activities: control of mRNA stability in the cytoplasm and transcriptional corepression in the nucleus (PMID:19276069, PMID:12756225). As an adaptor for mRNA decay, TOB1 uses its structured N-terminal BTG-Tob domain to bind the Caf1 deadenylase subunits CNOT7/CNOT8 of the CCR4-NOT complex, while its unstructured C-terminal region carries two PAM2 motifs that engage cytoplasmic poly(A)-binding protein PABPC1; by bridging these partners it recruits deadenylase activity to the 3' poly(A) tail and accelerates mRNA decay, localizing to P-bodies in doing so (PMID:17785442, PMID:19276069, PMID:20595394). This tethered deadenylation is the basis of its growth-suppressive role, and a Caf1-binding mutant loses antiproliferative activity (PMID:19276069, PMID:23236473); the activity directs decay of specific transcripts, including CPEB3-targeted mRNAs through a CPEB3-TOB1-Caf1 ternary complex and Id3 mRNA in embryonic stem cells (PMID:21336257, PMID:25951976). In a parallel nuclear pathway, TOB1 associates with receptor-regulated Smads (Smad1/5/8) and inhibitory Smads (Smad6/7) to suppress BMP/TGF-beta signaling, with Smad4/5-dependent ID2 induction restraining Th17 differentiation and intestinal inflammation, and it represses cyclin D1 transcription via histone deacetylase recruitment to act upstream of Rb (PMID:11163184, PMID:12782279, PMID:34920145, PMID:12756225, PMID:12050114). TOB1 function is gated by phosphorylation: ERK1/2 and p90rsk1 phosphorylate C-terminal serines (Ser152/154/164) to inactivate its antiproliferative output, and the deadenylation activity is separable from these sites (PMID:12050114, PMID:12151396, PMID:22252318). Its abundance is controlled by ubiquitin-proteasome turnover through Skp2-SCF and Cul4-DDB1(Cdt2) ligases, the latter antagonized by Cdc7 kinase to stabilize TOB1 during the DNA damage response and block apoptosis (PMID:16951159, PMID:23066029, PMID:18850001). Nucleocytoplasmic shuttling governed by an N-terminal NES and a bipartite NLS positions TOB1 for its cytoplasmic function, which requires cytoplasmic access (PMID:15235587, PMID:15051490).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Established TOB1 as a growth-suppressing protein and linked it to receptor tyrosine kinase signaling by identifying its physical association with ErbB2.

    Evidence GST pull-down, reciprocal Co-IP, and growth suppression assay in NIH3T3 cells

    PMID:8632892

    Open questions at the time
    • Did not define the biochemical mechanism of growth suppression
    • ErbB2 binding region mapped only to the C-terminal half
  2. 1999 Medium

    Connected TOB1 to the CCR4 deadenylase machinery and cell cycle control by mapping the Caf1 interaction to the N-terminal half.

    Evidence Co-IP and protein interaction assays with cell cycle analysis

    PMID:10602502

    Open questions at the time
    • Functional consequence of Caf1 binding for mRNA decay not demonstrated
    • Single lab, two methods
  3. 2000 High

    Defined a nuclear, signaling-suppressive function by showing TOB1 binds receptor-regulated Smads and restrains BMP-driven osteoblast proliferation in vivo.

    Evidence Co-IP, immunofluorescence, reporter assays, and tob knockout mouse bone phenotype

    PMID:11163184

    Open questions at the time
    • Whether Smad binding reflects corepressor activity at target promoters not resolved
    • Relationship to cytoplasmic deadenylation function unaddressed
  4. 2001 High

    Extended the Smad-associated function to immune quiescence, showing TOB1 enhances Smad DNA-binding at the IL-2 promoter to suppress T cell proliferation.

    Evidence Co-IP, EMSA, reporter assay, antisense loss-of-function and proliferation assays in T cells

    PMID:11694881

    Open questions at the time
    • Direct DNA contact by TOB1 vs Smad-mediated effect not separated
  5. 2001 Medium

    Began defining phospho-regulation of TOB1 by identifying p90rsk1 as a binding kinase downstream of receptor tyrosine kinases.

    Evidence In vitro kinase assay, Co-IP, chromatographic co-fractionation

    PMID:11260258

    Open questions at the time
    • In vivo phosphorylation evidence indirect
    • Functional readout of p90rsk1 phosphorylation not established
  6. 2002 High

    Established ERK1/2 phosphorylation of C-terminal serines as the switch that inactivates TOB1's antiproliferative function, placing TOB1 upstream of Rb via cyclin D1 suppression.

    Evidence In vitro kinase assay, S-to-A/S-to-E mutagenesis, transformation and proliferation assays, tob-/- cells, cyclin D1 analysis

    PMID:12050114 PMID:12151396

    Open questions at the time
    • Mechanism linking phosphorylation to loss of cyclin D1 repression not resolved
    • Whether phosphorylation affects deadenylation not addressed at this stage
  7. 2002 Medium

    Identified the C-terminal region as the determinant of TOB1's proteasomal instability, initiating the picture of regulated turnover.

    Evidence Proteasome inhibitor, ubiquitin co-expression, truncation/GFP-fusion stability assays

    PMID:12135500

    Open questions at the time
    • Responsible E3 ligase not identified
    • Degron sequence not mapped
  8. 2003 High

    Showed TOB1 acts as a transcriptional corepressor recruiting HDAC to the cyclin D1 promoter, with loss causing tumor predisposition.

    Evidence Reporter assay, Co-IP with HDAC, tob-/- tumor analysis, cyclin D1 mRNA measurement

    PMID:12756225

    Open questions at the time
    • Direct promoter occupancy by TOB1 not shown
    • Whether HDAC recruitment is Smad-dependent unclear
  9. 2003 High

    Broadened the Smad axis by showing TOB1 binds inhibitory Smads 6/7 and enhances Smad6 docking to BMP receptors to inhibit signaling.

    Evidence Yeast two-hybrid, Co-IP, colocalization, Xenopus embryo and BMP reporter assays

    PMID:12782279

    Open questions at the time
    • Quantitative contribution relative to R-Smad binding not resolved
  10. 2004 High

    Defined nucleocytoplasmic shuttling via an N-terminal NES and bipartite NLS and established that cytoplasmic access is required for antiproliferative activity.

    Evidence Leptomycin B, NES/NLS mutagenesis with strong exogenous signals, immunofluorescence, cell cycle analysis

    PMID:15051490 PMID:15235587

    Open questions at the time
    • Cytoplasmic target driving growth arrest not yet identified at this point
    • Regulation of shuttling by signaling incompletely defined
  11. 2005 High

    Linked TOB1 to translational control by showing it binds poly(A)-binding proteins and abrogates iPABP-enhanced IL-2 mRNA translation.

    Evidence Expression library screen, Co-IP, GST pull-down, in vitro translation, anergic T cell Co-IP

    PMID:15676026

    Open questions at the time
    • Whether the effect is on translation vs deadenylation not separated here
  12. 2007 High

    Unified the cytoplasmic mechanism, showing TOB1 simultaneously bridges CCR4-CAF1 and PABPC1 via distinct motifs to enhance deadenylation at P-bodies.

    Evidence GST pull-down, Co-IP, motif mutagenesis, Tet-off mRNA decay assay, immunofluorescence

    PMID:17785442

    Open questions at the time
    • In vivo target transcripts not yet identified
    • Quantitative kinetics of recruitment not measured
  13. 2009 High

    Provided structural resolution of the TOB1-Caf1 interface and showed complex formation, not Caf1 catalysis, is what matters for growth inhibition.

    Evidence X-ray crystallography of N-terminal TOB1 bound to hCaf1, plus mutant growth assays

    PMID:19276069

    Open questions at the time
    • Structure of the C-terminal PABPC1-binding region not in this work
  14. 2010 High

    Quantified the binding architecture and proposed a thermodynamic competition model for recruiting deadenylase to the poly(A) tail after translation termination.

    Evidence NMR spectroscopy, Western quantification, Kd determination

    PMID:20595394

    Open questions at the time
    • Competition model with eRF3 not validated in cells
    • Single lab
  15. 2011 High

    Demonstrated target-specific decay by showing TOB1 forms a CPEB3-TOB1-Caf1 ternary complex to accelerate deadenylation of CPEB3 target mRNAs.

    Evidence Co-IP, GST pull-down, in vitro deadenylation, dominant-negative mutants

    PMID:21336257

    Open questions at the time
    • Endogenous CPEB3 target transcripts not enumerated
  16. 2012 High

    Separated TOB1's two activities, showing tethered deadenylation depends on Caf1a/Caf1b and is independent of the ERK phosphorylation sites controlling antiproliferation.

    Evidence MS2 tethering and decay assays, subunit-specific siRNA, mutagenesis, proliferation and translation assays

    PMID:22252318 PMID:23236473

    Open questions at the time
    • How the two mechanisms are coordinated within a cell not resolved
  17. 2012 Medium

    Connected TOB1 to a tissue-level proliferative checkpoint by showing it binds Caf1 and Cdk1 in liver and restrains hepatocyte regeneration.

    Evidence Co-IP, kinase activity assay, Tob1-/- hepatectomy model

    PMID:20513747

    Open questions at the time
    • Direct vs deadenylation-mediated effect on Cdk1 unclear
    • Single lab
  18. 2012 High

    Identified the Cul4-DDB1(Cdt2) degradation route and its antagonism by Cdc7, linking TOB1 stability to survival during DNA damage.

    Evidence In vitro kinase assay, Co-IP, ubiquitination assay, Cdc7 siRNA, viability assay

    PMID:23066029

    Open questions at the time
    • Pro-apoptotic signals suppressed by stabilized TOB1 not fully defined
  19. 2006 High

    Identified Skp2-SCF as a primary E3 ligase for TOB1, coupling its degradation to cyclin D1 regulation.

    Evidence Co-IP, in vitro ubiquitination, Skp2-/- fibroblasts, siRNA, cyclin D1 assay

    PMID:16951159

    Open questions at the time
    • Phospho-dependence of Skp2 recognition not fully mapped
  20. 2014 Medium

    Established TOB1 as a stress-responsive node, showing its degradation underlies arsenite-induced inhibition of global mRNA deadenylation.

    Evidence siRNA phenocopy, poly(A) tail assay, protein degradation assay under arsenite

    PMID:25446091

    Open questions at the time
    • Protease responsible for stress degradation not identified
    • Single lab
  21. 2015 Medium

    Tied TOB1-driven decay to a specific developmental program by showing Id3 mRNA degradation limits embryonic stem cell proliferation.

    Evidence Tob1/Tob2 knockout ESCs, proliferation and Id3 mRNA stability assays

    PMID:25951976

    Open questions at the time
    • Whether Id3 is a direct vs indirect target not fully resolved
  22. 2021 High

    Linked the Smad axis to an in vivo immune phenotype, showing TOB1-Smad4/5 induce ID2 to restrain Th1/Th17 differentiation and protect against colitis.

    Evidence Co-IP, lentiviral perturbation, Tob1-/- colitis models, RNA-seq

    PMID:34920145

    Open questions at the time
    • Direct binding of TOB1-Smad complex at the ID2 locus not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the nuclear corepressor and cytoplasmic deadenylase functions are integrated, and what governs the choice between them in a given cell context, remains unresolved.
  • No unified model coordinating shuttling, phosphorylation state, and the two effector pathways
  • Genome-wide endogenous mRNA target set incompletely defined
  • Whether Smad/HDAC corepression and deadenylation regulate overlapping gene sets unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-168256 Immune System 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
CNOT7CNOT8CPEB3ERBB2PABPC1SKP2SMAD4SMAD6
Complex memberships
CCR4-NOT deadenylase complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 TOB1 was identified as a novel protein that physically interacts with the receptor tyrosine kinase p185erbB2 (ErbB2) via its C-terminal half, as demonstrated by GST pull-down and reciprocal co-immunoprecipitation. The interaction with kinase-active p185erbB2 hampers TOB1-mediated growth suppression of NIH3T3 cells. GST pull-down, reciprocal co-immunoprecipitation, cell growth assay Oncogene High 8632892
2000 TOB1 (Tob) negatively regulates BMP/Smad signaling in osteoblasts by associating with receptor-regulated Smads (Smad1, 5, and 8) and colocalizing with them in nuclear bodies upon BMP2 stimulation. Tob overexpression represses BMP2-induced, Smad-mediated transcriptional activation. Mice with targeted deletion of tob have increased bone mass due to increased osteoblast numbers and elevated BMP2-induced orthotopic bone formation. Co-immunoprecipitation, immunofluorescence colocalization, transcriptional reporter assays, tob knockout mouse analysis Cell High 11163184
2001 TOB1 associates with Smad2 and Smad4 in T cells and enhances Smad DNA-binding on the −105 negative regulatory element of the IL-2 promoter, thereby inhibiting IL-2 transcription and maintaining T cell quiescence. Forced expression of Tob inhibited T cell proliferation; antisense suppression augmented CD3-mediated responses. Co-immunoprecipitation, EMSA (Smad DNA-binding), transcriptional reporter assay, antisense oligonucleotide loss-of-function, proliferation assays Nature immunology High 11694881
1999 The N-terminal half of TOB1 (and Tob2) associates with human Caf1 (a component of the CCR4 transcription factor complex), and Caf1 in turn associates with cyclin-dependent kinases, implicating TOB1 in cell cycle regulation through this interaction. Co-immunoprecipitation, protein interaction assays, cell cycle analysis Oncogene Medium 10602502
2002 TOB1 is phosphorylated at Ser152, Ser154, and Ser164 by ERK1 and ERK2 upon growth factor stimulation. Non-phosphorylatable Tob (serine-to-alanine mutants) efficiently suppresses Ras-induced transformation and growth-factor-induced proliferation, while phosphomimetic mutants (serine-to-glutamate) are less inhibitory. Tob inhibits cell growth by suppressing cyclin D1 expression, and this is canceled by ERK1/2-mediated phosphorylation. Tob functions upstream of Rb. In vitro kinase assay, site-directed mutagenesis, cell proliferation and transformation assays, serum starvation experiments with tob−/− cells, cyclin D1 reporter/expression analysis Genes & development High 12050114
2002 TOB1 is identified as an ERK2-interacting protein and a substrate of ERK MAPK (ERK2) and JNK/SAPK (JNK2) in vitro. An ERK-docking site resides in the N-terminal portion of Tob; phosphorylation sites are in the C-terminal stretch. ERK phosphorylation negatively regulates Tob's anti-proliferative function. Two-hybrid screening, in vitro kinase assay, cell cycle analysis with phosphomimetic mutants The Journal of biological chemistry High 12151396
2001 p90rsk1 associates with and phosphorylates TOB1 on serines and threonines in vitro and in vivo, suggesting p90rsk1 (downstream of receptor tyrosine kinases) regulates Tob function through phosphorylation. In vitro kinase assay, co-immunoprecipitation, chromatographic co-fractionation Genes to cells Medium 11260258
2003 TOB1 acts as a transcriptional corepressor by suppressing cyclin D1 promoter activity through an interaction with histone deacetylase. Tob knockout mice are prone to spontaneous tumor formation, and cyclin D1 mRNA is increased in the absence of Tob. Transcriptional reporter assay, co-immunoprecipitation with HDAC, tob−/− mouse tumor analysis, cyclin D1 mRNA measurement Genes & development High 12756225
2003 TOB1 interacts with inhibitory Smads 6 and 7 (identified by yeast two-hybrid screen), colocalizes with Smad6 at the plasma membrane, and enhances the interaction between Smad6 and activated BMP type I receptors, thereby inhibiting BMP signaling. Tob and Tob2 cooperate with Smad6 to inhibit BMP signaling in Xenopus embryonic explants and mammalian cells. Yeast two-hybrid screen, co-immunoprecipitation, immunofluorescence colocalization, Xenopus embryo assay, BMP reporter assay Mechanisms of development High 12782279
2004 TOB1 is a nuclear protein imported via a nuclear localization signal (NLS). Mutation of the NLS impairs nuclear localization and antiproliferative activity. In oncogenic ErbB2-transformed cells, nuclear export of Tob is facilitated through a nuclear export signal (NES), reducing antiproliferative activity. NLS/NES mutagenesis, immunofluorescence microscopy, cell cycle analysis Oncogene High 15235587
2004 TOB1 contains a functional NES in residues 2–14 and a bipartite NLS in residues 18–40, enabling nucleocytoplasmic shuttling. Cytoplasmic localization or nucleocytoplasmic shuttling (rather than strict nuclear localization) is important for the antiproliferative function of Tob, as addition of a strong NLS weakens its cell cycle inhibitory activity. Leptomycin B treatment, NES/NLS mutagenesis with exogenous strong NLS/NES constructs, cell cycle analysis Experimental cell research High 15051490
2005 TOB1 interacts with poly(A)-binding protein (PABP) and inducible PABP (iPABP) through the C-terminal region of iPABP. Tob abrogates iPABP-enhanced translation of IL-2 mRNA in vitro and suppresses IL-2 production in cells. Tob was co-immunoprecipitated with iPABP from anergic human T cells. Expression library screening, co-immunoprecipitation, GST pull-down, in vitro translation assay, overexpression in NIH3T3 cells Genes to cells High 15676026
2006 TOB1 is degraded via the ubiquitin-proteasome pathway through Skp2, an F-box substrate-targeting subunit of the SCF ubiquitin ligase complex. Skp2 interacts with Tob1 and facilitates its ubiquitination in intact cells and in vitro. F-box or LRR deletion mutants of Skp2 neither bind nor ubiquitinate Tob1. Tob1 is stabilized in Skp2−/− cells. Co-immunoprecipitation, in vitro ubiquitination assay, Skp2 knockout fibroblasts, Skp2 knockdown (siRNA), cyclin D1 expression assay Cancer research High 16951159
2002 TOB1 (and BTG1, BTG2, Tob2) are degraded by the ubiquitin-proteasome system. The C-terminal region of Tob is necessary and sufficient to confer instability; C-terminal truncation stabilizes the protein. Proteasome inhibitor treatment, co-expression with ubiquitin, truncation mutant analysis, GFP fusion stability assay European journal of biochemistry Medium 12135500
2007 Human TOB1 enhances mRNA deadenylation in vivo by simultaneously interacting with the CCR4-CAF1 deadenylase complex and cytoplasmic poly(A)-binding protein PABPC1 via distinct protein motifs. Interaction with PABPC1 is necessary for TOB1's deadenylation-enhancing effect. TOB1 colocalizes with P-bodies as shown by immunofluorescence. GST pull-down, co-immunoprecipitation, mutagenesis mapping of interaction motifs, mRNA decay assay (Tet-off pulse-chase), immunofluorescence microscopy Molecular and cellular biology High 17785442
2008 TOB1 associates with the CCR4-NOT deadenylase complex; the C-terminal half of Tob interacts with Cnot1 (core protein of CCR4-NOT). Tob suppresses the deadenylase activity associated with the CCR4-NOT complex in vitro. Proteomics (stable cell line + mass spectrometry), co-immunoprecipitation, in vitro deadenylase activity assay Cancer science Medium 18377426
2009 Crystal structure of the N-terminal region of TOB1 bound to human Caf1 (hCaf1) was determined. Tob exhibits a novel fold; hCaf1 resembles yeast Pop2 and human PARN catalytic domain. Both Box A and Box B of Tob mediate the association with hCaf1. The deadenylase activity of Caf1 is not critical, but complex formation between Tob and Caf1 is crucial for cell growth inhibition. Caf1 tethers Tob to the CCR4-Not complex, and Tob gathers poly(A)-binding proteins at its C-terminal region to exert antiproliferative activity. X-ray crystallography, cell growth assays with wild-type and mutant proteins, protein interaction analysis The Journal of biological chemistry High 19276069
2010 Quantitative NMR and biochemical analyses revealed that Tob consists of a structured N-terminal BTG-Tob domain (which binds Caf1) and an unstructured C-terminal region containing two PAM2 motifs (which bind PABPC1 PABC domain with Kd ~20 µM). Given that cellular eRF3 levels (~4–5 µM) exceed Tob levels (<0.2 µM), a thermodynamic competition model was proposed in which Tob-Caf1 recruits deadenylase to the poly(A) tail following translation termination. NMR spectroscopy, Western blot quantification, binding affinity measurement (Kd determination) The Journal of biological chemistry High 20595394
2011 TOB1 binds directly to CPEB3 (a sequence-specific RNA-binding protein) via the C-terminal RNA-binding domain of CPEB3 interacting with the C-terminal unstructured region of Tob. Tob then recruits Caf1 deadenylase to form a CPEB3-Tob-Caf1 ternary complex, mediating accelerated deadenylation and decay of CPEB3 target mRNA. Dominant-negative mutants of either Caf1 or Tob abrogated CPEB3-accelerated deadenylation. Co-immunoprecipitation, GST pull-down, in vitro deadenylation assay, dominant-negative mutant analysis The EMBO journal High 21336257
2012 The anti-proliferative activity of TOB1 (and BTG/TOB family members) is mediated through interactions with Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-Not complex. Surface-exposed residues of TOB1 mediating this interaction were characterized, and a Caf1a/Caf1b-binding mutant of TOB1 lost anti-proliferative activity. TOB1 regulation of mRNA abundance and translation is also dependent on Caf1a/Caf1b but not on Ccr4a/Ccr4b or non-catalytic CNOT1/CNOT3 subunits. Site-directed mutagenesis, cell proliferation assays, mRNA abundance assay, translation assay, siRNA knockdown of Ccr4-Not subunits PloS one High 23236473
2012 TOB1 tethering to mRNA directly promotes mRNA deadenylation via recruitment of CAF1-CCR4; this activity is independent of the three ERK phosphorylation serines that regulate antiproliferative activity, suggesting TOB1 arrests cell growth through at least two distinct mechanisms. TOB1 and TOB2 are functionally interchangeable in deadenylation. Tethering assay (MS2-based), mRNA deadenylation and decay monitoring, phosphorylation site mutagenesis, cell growth assay Molecular and cellular biology High 22252318
2012 TOB1 associates directly with Caf1 and Cdk1 (cyclin-dependent kinase 1) in the liver, and modulates Cdk1 kinase activity. Tob1 protein decreases after 2/3 hepatectomy via posttranscriptional mechanisms, and deletion of Tob1 accelerates liver regeneration and hepatocyte proliferation. Co-immunoprecipitation, kinase activity assay, Tob1−/− mouse hepatectomy model, hepatocyte proliferation assay The Journal of experimental medicine Medium 20513747
2001 PMA-induced phosphorylation of MARCKS increases its binding affinity to TOB1, competing with ErbB2 for TOB1 binding, resulting in decreased Tob–ErbB2 interaction and subsequent ErbB2 activation in breast cancer cells. Co-immunoprecipitation, PMA stimulation assay, domain mapping (PSD of MARCKS) Biochemical and biophysical research communications Medium 11327693
2005 TOB1 and Tob2 suppress steroid hormone receptor-dependent transcriptional activation in osteoblastic cells. TOB1 inhibits nuclear foci formation of dihydrotestosterone-bound androgen receptor (AR), as visualized by GFP-AR confocal microscopy. This effect does not require the LXXLL motif in Tob. Luciferase reporter assay, GFP-AR live-cell confocal microscopy, mutagenesis of LXXLL motif Molecular and cellular endocrinology Medium 15664454
2008 TOB1 activates the mouse Dpp2 (dipeptidyl peptidase 2) promoter in concert with KLF2, suggesting TOB1 functions as a transcriptional co-activator in the context of lymphocyte quiescence maintenance. Promoter-reporter assay (luciferase), endogenous transcript measurement Molecular immunology Low 18555530
2012 Cdc7 (DNA replication-initiating kinase) phosphorylates TOB1 and interacts with it to inhibit Cul4-DDB1(Cdt2)-dependent ubiquitination and proteasomal degradation of Tob. In response to mild DNA damage, Tob levels increase through both transcription and Cdc7-mediated protein stabilization, and this inhibits pro-apoptotic signaling. Cells lacking Cdc7 show increased Tob ubiquitination and undergo apoptosis after mild DNA damage. In vitro kinase assay, co-immunoprecipitation, ubiquitination assay, siRNA knockdown of Cdc7, cell viability assay The Journal of biological chemistry High 23066029
2008 Proteasome-dependent degradation of TOB1 triggered by UV irradiation is required for UV-induced apoptosis. Degradation-resistant Tob (with short C-terminal deletions or a tag sequence) impairs UV-induced apoptosis. siRNA knockdown of Tob results in frequent apoptosis even at sub-apoptotic UV doses in a p53-independent manner. tob−/− mice and MEFs are hypersensitive to UV irradiation. Proteasome inhibitor assay, C-terminal deletion/tag mutants, siRNA knockdown, tob−/− mouse/MEF analysis, apoptosis assays Oncogene High 18850001
2014 Arsenite-induced oxidative stress inhibits mRNA deadenylation primarily through proteolytic degradation of TOB1 (and Pan3). siRNA knockdown of Tob and Pan3 recapitulates global stabilization of the mRNA poly(A) tail observed during arsenite stress, establishing Tob as a critical mediator of stress-induced deadenylation inhibition. siRNA knockdown, poly(A) tail length assay, protein degradation assay, arsenite treatment Biochemical and biophysical research communications Medium 25446091
2015 TOB1 and TOB2 inhibit proliferation of mouse embryonic stem cells via degradation of Id3 mRNA (a BMP4-signaling target). Tob1−/−, Tob2−/−, and Tob1/2 double KO ESCs grew faster than wild-type ESCs without losing pluripotency. Knockout ESC generation, proliferation assay, mRNA stability/abundance measurement for Id3 Biochemical and biophysical research communications Medium 25951976
2021 TOB1 associates with Smad4/5 to induce expression of ID2, which in turn restrains Th1/Th17 cell differentiation, thereby blocking intestinal mucosal inflammation in IBD. Tob1−/− mice showed severe colitis; reconstitution with Tob1−/− CD4+ T cells recapitulated this. RNA sequencing identified ID2 as the functional target of TOB1. Co-immunoprecipitation (TOB1-Smad4/5), lentiviral overexpression/knockdown, Tob1−/− mouse colitis models (TNBS enema, Rag1−/− reconstitution), RNA sequencing Cellular and molecular gastroenterology and hepatology High 34920145
1997 Tob1 protein is localized to the nucleus and contains a sequence rich in proline and glutamine typical of transcription factors. The mouse tob gene lacks introns in its coding region and is ubiquitously expressed. The ATTTA motif in the 3'-UTR is characteristic of immediate early genes. Molecular cloning, Northern blot, sequence analysis Gene Low 9210596
2015 TOB1 localization is mainly cytoplasmic in pancreatic cancer cells. Foxa2 overexpression significantly enhanced TOB1 promoter activity by binding to the TOB1 promoter (luciferase reporter assay), placing Foxa2 as a transcriptional activator of TOB1. Dual-luciferase reporter assay, immunofluorescence localization Cancer medicine Low 31891232
2015 TOB1 is associated with P-body marker Dcp2 in round spermatids and oocytes, as shown by co-immunofluorescence and protein co-expression analysis. TOB1 protein is highly expressed in round spermatids and oocytes, consistent with a post-transcriptional regulatory role in germ cells. Immunofluorescence, RT-ddPCR, co-localization microscopy 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 247 19746446
2001 Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nature immunology 224 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 197 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 103 22496419
2003 Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes & development 101 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 85 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
2020 Exosomal miRNA-486-5p derived from rheumatoid arthritis fibroblast-like synoviocytes induces osteoblast differentiation through the Tob1/BMP/Smad pathway. Biomaterials science 74 32406432
2002 Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects. Genes to cells : devoted to molecular & cellular mechanisms 73 11856371
2011 Anti-proliferative protein Tob negatively regulates CPEB3 target by recruiting Caf1 deadenylase. The EMBO journal 69 21336257
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 64 23236473
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
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
2017 Three TOB1-related YABBY genes are required to maintain proper function of the spikelet and branch meristems in rice. The New phytologist 51 28556940
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
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
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 35 32307083
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
2019 MiR-32-5p Regulates Radiosensitization, Migration And Invasion Of Colorectal Cancer Cells By Targeting TOB1 Gene. OncoTargets and therapy 33 31814731
2008 Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex. Cancer science 32 18377426
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 29 26824451
2017 MicroRNA-590 promotes pathogenic Th17 cell differentiation through targeting Tob1 and is associated with multiple sclerosis. Biochemical and biophysical research communications 28 28947212
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
2021 Identification of miR‑25‑3p as a tumor biomarker: Regulation of cellular functions via TOB1 in breast cancer. Molecular medicine reports 15 33786619
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
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
2014 Arsenite inhibits mRNA deadenylation through proteolytic degradation of Tob and Pan3. Biochemical and biophysical research communications 11 25446091
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
2013 Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway. Oncology reports 10 23756562
2023 Chimeric Tobramycin-Based Adjuvant TOB-TOB-CIP Potentiates Fluoroquinolone and β-Lactam Antibiotics against Multidrug-Resistant Pseudomonas aeruginosa. ACS infectious diseases 9 36917096
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

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