Affinage

TUBB3

Tubulin beta-3 chain · UniProt Q13509

Length
450 aa
Mass
50.4 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TUBB3 (βIII-tubulin) is a β-tubulin isotype that incorporates into microtubules and couples axon guidance receptor signaling to growth cone microtubule dynamics; normal TUBB3 is required for axon guidance, and disease-causing missense mutations alter microtubule dynamic instability and microtubule–kinesin interactions to produce axon guidance defects and cortical malformations (PMID:20074521, PMID:20829227). At the growth cone, TUBB3 directly binds the netrin-1 receptors DCC, DSCAM, and UNC5C in polymerized microtubules, and netrin-1 bidirectionally tunes these contacts — increasing TUBB3 association with the attractive receptors DCC and DSCAM to drive outgrowth, attraction and branching, while decreasing the TUBB3–UNC5C interaction during repulsion (PMID:23641072, PMID:28483977, PMID:25754961). Disease-associated TUBB3 mutants such as R262C, A302V and R62Q lose netrin-1–induced DCC binding and netrin-1–modulated UNC5C binding and disrupt both attractive and repulsive guidance in vitro and in vivo, linking the receptor–microtubule interface directly to the mutant phenotypes (PMID:29382549, PMID:31226147). Although TUBB3 is dispensable for viability because other β-tubulin isotypes compensate, it confers a non-redundant role in growth cone microtubule dynamics and the rate of peripheral axon regeneration (PMID:30110642). TUBB3 is regulated by post-translational phosphorylation in dividing cells: Citron kinase recruits CK2α to phosphorylate TUBB3 at Ser444 to stabilize midbody microtubules during cytokinesis, and c-SRC phosphorylates Tyr340 to control TUBB3 stability and mitotic spindle function (PMID:26586574, PMID:35631517). TUBB3 transcription is directly controlled by the androgen receptor through intronic androgen response elements, by ALDH1A1-derived retinoic acid through promoter RAREs, and by the ZFP64 transcription factor, and is further set by CpG-island methylation and histone acetylation (PMID:21734264, PMID:31187490, PMID:39706253, PMID:18497984). In cancer, TUBB3 acts within a TUBB3/PTEN/AKT axis and an αvβ3/FAK/Src axis to promote anoikis resistance and aggressive tumor behavior (PMID:25414139, PMID:31412591, PMID:38809199). While TUBB3 modulates microtubule responses to microtubule-targeting agents such as epothilones, robust overexpression from the endogenous locus has only a marginal direct effect on taxol sensitivity, with mechanisms such as P-glycoprotein dominating resistance (PMID:23321512, PMID:29069726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2010 High

    Establishing whether TUBB3 mutations act through microtubule dynamics answered why heterozygous missense changes cause neurodevelopmental disease.

    Evidence In vitro heterodimer formation, yeast tubulin mutagenesis, and a knock-in mouse with axon guidance readouts

    PMID:20074521

    Open questions at the time
    • Did not resolve how altered dynamics translate into receptor-level guidance defects
    • Cortical migration was spared in this model, leaving the basis of cortical phenotypes open
  2. 2010 Medium

    Distinguishing cortical-malformation mutations from CFEOM3 mutations clarified that opposite effects on microtubule stability underlie different TUBB3 phenotypes.

    Evidence Heterodimer formation in mammalian cells and depolymerization-resistance assays in patient fibroblasts

    PMID:20829227

    Open questions at the time
    • Single-lab cellular assays without in vivo confirmation
    • Mechanistic link from depolymerization resistance to specific malformation not defined
  3. 2013 High

    Identifying a direct TUBB3–DCC interaction connected netrin-1 attractive signaling to microtubule dynamics at the growth cone.

    Evidence Co-IP, cosedimentation, neuronal knockdown with outgrowth/attraction readouts, and in vivo commissural projection assay

    PMID:23641072

    Open questions at the time
    • Binding interface on TUBB3 and DCC not mapped
    • How netrin-1 mechanistically induces the interaction unresolved
  4. 2015 High

    Showing DSCAM and DCC cooperate via TUBB3 explained how multiple attractive receptors converge on the microtubule cytoskeleton during axon branching.

    Evidence Co-IP, cosedimentation, neuronal knockdown with branching readout, and Src-family kinase blockade

    PMID:25754961

    Open questions at the time
    • Role of Src-family kinases in the interaction not mechanistically dissected
    • Stoichiometry of the DSCAM/DCC/TUBB3 assembly unknown
  5. 2017 High

    Demonstrating that netrin-1 reduces a direct TUBB3–UNC5C interaction established a microtubule-based mechanism for repulsive guidance distinct from attraction.

    Evidence Co-IP, cosedimentation, knockdown with repulsion readouts, in vivo DRG projection, and EB3-GFP live imaging

    PMID:28483977

    Open questions at the time
    • How a single isotype produces opposite outcomes via different receptors not fully explained
    • Downstream effectors translating dynamics into collapse not identified
  6. 2018 High

    Testing disease mutants against the DCC interaction linked the receptor–microtubule interface directly to attractive guidance pathology.

    Evidence Co-IP, colocalization, cosedimentation, and in vitro/in ovo guidance assays across twelve mutants

    PMID:29382549

    Open questions at the time
    • Not all disease mutants disrupt DCC binding, leaving alternative mechanisms for some
    • Structural basis of reduced binding not determined
  7. 2018 High

    A clean TUBB3 knockout resolved redundancy versus non-redundancy, showing isotype compensation for viability but a specific requirement in axon regeneration rate.

    Evidence Knockout mouse, growth cone dynamics imaging, in vitro/in vivo neurite outgrowth, and proteomics of β-tubulin isotypes

    PMID:30110642

    Open questions at the time
    • Molecular basis of the non-redundant dynamics function not isolated
    • Relationship between regeneration phenotype and guidance receptor binding untested
  8. 2019 High

    Mapping mutant effects on the UNC5C interaction extended the receptor-binding pathology model to repulsive guidance.

    Evidence Co-IP, cosedimentation, immunofluorescence, and in vitro/in ovo repulsion assays across twelve mutants

    PMID:31226147

    Open questions at the time
    • Subset specificity of mutants for DCC versus UNC5C not mechanistically explained
  9. 2015 High

    Identifying Ser444 phosphorylation by a Citron kinase–recruited CK2α revealed a cytokinesis role for TUBB3 in dividing CNS progenitors.

    Evidence Co-IP, phospho-analysis, phospho-mutant rescue, and midbody immunofluorescence

    PMID:26586574

    Open questions at the time
    • How S444 phosphorylation alters microtubule stability biochemically unresolved
    • Generality beyond CIT-K-dependent cells not established
  10. 2022 Medium

    Identifying c-SRC phosphorylation of Tyr340 connected a kinase to TUBB3 protein stability and spindle function.

    Evidence In vitro kinase assays, phospho-specific analysis, SRC inhibition, fractionation, and spindle immunofluorescence

    PMID:35631517

    Open questions at the time
    • Single-lab phospho-site characterization
    • Mechanism linking Y340 to stability not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TUBB3's transcriptional regulators, post-translational modifications, and cancer signaling axes integrate with its core role in microtubule dynamics remains unresolved.
  • No structural model of receptor–TUBB3 or motor–TUBB3 interfaces
  • Causal link between cancer TUBB3/PTEN/AKT roles and its microtubule-dynamics function not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0005198 structural molecule activity 3
Localization
GO:0005856 cytoskeleton 3 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2
Partners
CITCSNK2A1DCCDSCAMEHD1KIF21ASRCUNC5C
Complex memberships
microtubule

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Eight heterozygous missense mutations in TUBB3 impair tubulin heterodimer formation in vitro, though folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter microtubule dynamic instability, whereas a subset disrupts the interaction of microtubules with kinesin motors. A knock-in disease mouse model reveals axon guidance defects without cortical cell migration abnormalities, establishing that normal TUBB3 is required for axon guidance and maintenance. In vitro tubulin heterodimer formation assays, yeast tubulin mutagenesis modeling, knock-in mouse model with axon guidance phenotype readout Cell High 20074521
2010 Novel TUBB3 missense mutations causing malformations of cortical development reduce heterodimer formation yet produce correctly formed microtubules in mammalian cells, and alter resistance of microtubules to depolymerization in patient fibroblasts. This contrasts with CFEOM3-related mutations which increase microtubule stability, indicating that distinct effects on microtubule dynamics underlie different TUBB3-related phenotypes. Heterodimer formation assays in mammalian cells, microtubule depolymerization assays in patient fibroblasts Human molecular genetics Medium 20829227
2013 TUBB3 directly interacts with the netrin-1 receptor DCC, and netrin-1 induces this interaction in primary neurons. TUBB3 colocalizes with DCC in growth cones, microtubule dynamics are required for netrin-1-promoted TUBB3–DCC association, netrin-1 increases co-sedimentation of DCC with polymerized microtubules, and knockdown of TUBB3 inhibits netrin-1-induced microtubule dynamics, axon outgrowth and attraction in vitro, and causes commissural axon projection defects in vivo. Co-immunoprecipitation, cosedimentation assay, primary neuron knockdown with axon outgrowth/attraction readouts, in vivo commissural axon projection assay Journal of cell science High 23641072
2017 TUBB3 directly interacts with the netrin-1 repulsive receptor UNC5C, partially colocalizes with UNC5C in the peripheral growth cone, and netrin-1 reduces this interaction. UNC5C interacts with polymerized TUBB3 in microtubules; netrin-1 decreases this interaction. Knockdown of either TUBB3 or UNC5C blocks netrin-1-promoted axon repulsion in vitro and causes defects in dorsal root ganglion axon projection in vivo. Live-cell EB3-GFP imaging shows netrin-1 increases microtubule dynamics differentially in the growth cone during repulsion, and TUBB3 knockdown abolishes this effect. Co-immunoprecipitation, in vitro cosedimentation assay, primary neuron knockdown, in vivo axon projection assay, live-cell EB3-GFP imaging The Journal of neuroscience High 28483977
2015 TUBB3 directly interacts with the Netrin-1 receptor DSCAM, and Netrin-1 increases this interaction in primary neurons requiring microtubule dynamics. DSCAM and DCC interdependently coordinate binding to TUBB3; Src family kinases are required for DSCAM–TUBB3 binding. Knockdown of DSCAM, DCC, or TUBB3 each blocks Netrin-1-induced axon branching of cortical neurons, establishing that DSCAM collaborates with DCC via TUBB3 to regulate microtubule dynamics in axon branching. Co-immunoprecipitation, cosedimentation assay, primary neuron knockdown with axon branching readout, function-blocking antibody Neuroscience High 25754961
2018 Eight out of twelve disease-associated TUBB3 missense mutants show significantly reduced interaction with DCC compared to wild-type TUBB3. Mutants R262C and A302V exhibit decreased colocalization with DCC in growth cones, fail to show netrin-1-induced DCC binding in primary neurons, and fail to show netrin-1-induced co-sedimentation of DCC with polymerized microtubules. Expression of R262C or A302V suppresses netrin-1-induced neurite outgrowth, branching and attraction in vitro and causes commissural axon projection defects in ovo. Co-immunoprecipitation with TUBB3 mutants, immunofluorescence colocalization in growth cones, cosedimentation assay, in vitro axon outgrowth/attraction assays, in ovo spinal cord axon projection assay Neuroscience High 29382549
2019 Five of twelve disease-associated TUBB3 missense mutants show significantly reduced interaction with UNC5C. Mutants R262C and R62Q show decreased colocalization with UNC5C in growth cones and fail to show netrin-1-reduced cosedimentation of UNC5C with polymerized microtubules. Expression of R262C or R62Q blocks netrin-1-induced growth cone collapse and axonal repulsion in vitro and causes DRG axon projection defects in ovo, establishing that TUBB3 mutations perturb netrin-1/UNC5C repulsive signaling. Co-immunoprecipitation with TUBB3 mutants, cosedimentation assay, immunofluorescence, in vitro repulsion assays, in ovo axon projection assay PloS one High 31226147
2015 Citron kinase (CIT-K) modulates stability of midbody microtubules through TUBB3, which is expressed in proliferating CNS progenitors. Depletion of TUBB3 in CIT-K-dependent cells confers resistance to CIT-K loss; TUBB3 overexpression increases sensitivity to CIT-K knockdown. CIT-K loss decreases phosphorylation of TUBB3 at Ser444, a stabilizing post-translational modification. CIT-K interacts with TUBB3 and recruits CK2α to the midbody to phosphorylate S444. Non-phosphorylatable TUBB3 S444A causes cytokinesis failure; phospho-mimetic S444D rescues cytokinesis failure induced by CIT-K or CK2α loss. siRNA knockdown, overexpression, Co-immunoprecipitation (CIT-K/TUBB3/CK2α), phosphorylation analysis, phospho-mutant rescue experiments, immunofluorescence of midbody Cell death and differentiation High 26586574
2022 TUBB3 is phosphorylated at Tyrosine 340 (Y340) by c-SRC in prostate cancer cells. Y340 phosphorylation regulates TUBB3 protein stability and subcellular localization. Inhibition of SRC kinase compromises mitotic spindle stability, at least partly due to lack of TUBB3 Y340 phosphorylation. In vitro kinase assays, phospho-specific analysis, SRC inhibitor treatment, subcellular fractionation/localization, mitotic spindle immunofluorescence Pharmaceutics Medium 35631517
2018 Tubb3 knockout mice show no neurobehavioral or neuropathological deficits; upregulation of other β-tubulin isotypes compensates to maintain equivalent total β-tubulin levels. However, adult DRG neurons lacking TUBB3 have decreased growth cone microtubule dynamics and a 22% decreased neurite outgrowth rate in vitro and in vivo, establishing a specific role for TUBB3 in the rate of peripheral axon regeneration that cannot be replaced by other β-tubulins. Knockout mouse generation, neurobehavioral phenotyping, live-imaging of growth cone microtubule dynamics, in vitro and in vivo neurite outgrowth rate measurement, quantitative proteomics of β-tubulin isotypes Cell reports High 30110642
2014 βIII-tubulin (TUBB3) suppression in NSCLC cells alters cell morphology, reduces tumor spheroid outgrowth, and increases sensitivity to anoikis. The PTEN/AKT signaling axis was defined as a critical pathway regulated by TUBB3 in NSCLC cells, and TUBB3 knockdown reduces tumor incidence and growth in vivo. siRNA knockdown, differential proteomics, anoikis resistance assays, spheroid outgrowth assays, in vivo xenograft, PTEN/AKT pathway analysis Cancer research Medium 25414139
2019 EHD1 interacts with TUBB3 (identified by mass spectrometry) and modulates microtubule stability through this interaction. TUBB3 depletion significantly attenuates EHD1-induced EGFR-TKI resistance and EMT in NSCLC cells, placing TUBB3 downstream of EHD1 in the IL-1β/EHD1/TUBB3 axis regulating resistance. Mass spectrometry interactome, co-immunoprecipitation, siRNA knockdown, microtubule stability assays, cell sensitivity assays Oncogene Medium 31740781
2021 ALDH1A1-mediated retinoic acid synthesis activates TUBB3 transcription through functional retinoic acid response elements (RAREs) identified in the TUBB3 promoter. TUBB3 knockdown suppresses bladder cancer patient-derived cell (PDC) proliferation and spheroid formation, establishing TUBB3 as a downstream transcriptional target of the ALDH1A1/retinoic acid pathway in cancer stem-like cells. RARE identification in TUBB3 promoter, luciferase reporter assay, ALDH1A1 shRNA knockdown, TUBB3 shRNA knockdown, PDC spheroid assays, in vivo xenograft International journal of cancer Medium 31187490
2010 The human MC1R gene has a highly complex and inefficient poly(A) site that allows intergenic splicing between MC1R and its immediate downstream neighbour TUBB3. These chimeric MC1R-TUBB3 transcripts produce two distinct protein isoforms (Iso1 and Iso2) that localize to the plasma membrane and endoplasmic reticulum. Treatment with α-MSH or activation of p38-MAPK shifts expression from canonical MC1R toward chimeric MC1R-TUBB3 isoforms in human melanocytes. RT-PCR detection of chimeric transcripts, poly(A) site analysis, immunofluorescence localization of isoforms, α-MSH and p38-MAPK pathway activation assays Nucleic acids research Medium 21071418
2015 MC1R-TUBB3 chimeric isoforms (Iso1, Iso2) show strongly reduced plasma membrane expression compared to wild-type MC1R due to aberrant forward trafficking rather than high endocytosis rates. Both isoforms bind radiolabeled agonist with same affinity as MC1R-001 but show lower functional coupling to cAMP while ERK activation upon αMSH binding is unimpaired, indicating imbalanced signaling. Heterodimerization of MC1R-001 with the splice isoforms (confirmed by co-immunoprecipitation) causes decreased surface expression of binding sites. Heterologous expression, radioligand binding assay, cAMP functional assay, ERK phosphorylation assay, trafficking analysis, co-immunoprecipitation PloS one Medium 26657157
2011 Androgen receptor (AR) directly regulates Tubb3 expression in Sertoli cells. Two androgen response elements (AREs) in Tubb3 intron 1 bind AR in vitro; mutation of ARE1 strongly reduces androgen-dependent reporter gene expression; AR binds the Tubb3 ARE region in vivo (ChIP). Tubb3 is uniquely regulated by AR among β-tubulin genes in the testis. SCARKO mouse model, in silico ARE identification, in vitro ARE binding assay, ARE mutation reporter assay, ChIP (AR binding at Tubb3 locus in vivo), RT-PCR expression analysis Biology of reproduction Medium 21734264
2013 Loss of TUBB3 enhances the action of epothilones in lung and breast cancer cells: TUBB3 knockdown increased the severity of drug-induced mitotic defects and resulted in stabilisation of microtubule dynamics. Exogenous TUBB3 expression in an epothilone-resistant cell line conferred response to drug treatments. Reduced levels of TUBB2A-C or TUBB had no apparent effect, establishing specificity for TUBB3 in the epothilone response through its impact on microtubule dynamics. siRNA knockdown, overexpression in resistant cell line, live cell microscopy for mitotic defects and microtubule dynamics, cell proliferation assays British journal of cancer Medium 23321512
2023 OSGIN1 interacts with TUBB3 (identified by IP-MS/MS and confirmed by Co-IP and proximity ligation assay) and enhances DYRK1A-mediated phosphorylation of TUBB3 at serine 172, which is critical for inducing tubulin depolymerization. OSGIN1 knockdown strongly increases tubulin polymerization and re-establishes gefitinib sensitivity in vitro and in vivo. IP-MS/MS, co-immunoprecipitation, proximity ligation assay, tubulin polymerization assay, phospho-proteomics, NSCLC patient-derived xenograft, siRNA knockdown Cellular and molecular life sciences Medium 37646890
2024 TUBB3 inhibition suppresses PD-L1 expression through the EMT-related SNAI1 transcription factor, and TUBB3 knockdown enhances cytotoxic T cell killing of lung cancer cells. TUBB3 was identified as a resistance gene in in vivo genome-wide CRISPR screening; TUBB3 expression is elevated in anti-PD-1 non-responders and in resistant cells. In vivo genome-wide CRISPR screen, small molecule TUBB3 inhibitor treatment, anti-PD-1 combination assay, cytotoxic T cell killing assay, PD-L1/SNAI1 pathway analysis Neoplasia Medium 39671912
2019 TUBB3 knockdown in prostate cancer cells enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression, establishing a reciprocal negative regulatory relationship. PI3K inhibitor (LY294002) suppressed TUBB3 expression and re-sensitized docetaxel-resistant and cabazitaxel-resistant cell lines to their respective drugs, placing TUBB3 functionally within the PI3K/AKT pathway in taxane resistance. shRNA knockdown, PTEN knockout, PI3K inhibitor treatment, drug sensitivity assays (DTX, CBZ), Western blot International journal of molecular sciences Medium 31412591
2019 RILPL2 interacts with TUBB3 in breast cancer cells; this interaction promotes destabilization of TUBB3, downregulates TUBB3 protein, and upregulates PTEN expression. RILPL2 overexpression inhibits BC cell proliferation and metastasis in vitro and in vivo, and reverses taxotere resistance via the TUBB3/PTEN/AKT pathway. Co-immunoprecipitation (exogenous RILPL2 with TUBB3), overexpression, in vitro and in vivo cell proliferation/metastasis assays, PTEN/AKT pathway analysis American journal of cancer research Low 31497344
2024 TUBB3 depletion significantly reverses anoikis resistance in prostate cancer cells during ECM detachment and reduces αvβ3/FAK/Src axis activation, blocking downstream oncogenic signaling. Bone-targeting lipid nanoparticle delivery of siTUBB3 significantly attenuated PCa bone metastasis progression in vivo. shRNA/siRNA knockdown, anoikis resistance assays, αvβ3/FAK/Src pathway analysis by Western blot, in vivo bone metastasis model with siRNA nanoparticle delivery Advanced healthcare materials Medium 38809199
2025 KIF21A variant p.Leu664Pro shows decreased binding to TUBB3 in vitro by co-immunoprecipitation. This disrupted KIF21A–TUBB3 interaction is associated with a peripheral neuropathy phenotype distinct from classic CFEOM, establishing that the KIF21A–TUBB3 physical interaction is required for normal KIF21A function in axon maintenance. Co-immunoprecipitation of KIF21A variant vs. reference with TUBB3, protein structural modelling Journal of medical genetics Low 39643435
2023 NOTCH3 binds TUBB3 (by co-immunoprecipitation confirmed by mass spectrometry) and activates the MAPK signaling pathway in docetaxel-resistant prostate cancer cells. NOTCH3 promotes stemness, lipid metabolism, and docetaxel resistance via TUBB3 and MAPK pathways; MEF2A directly regulates NOTCH3 transcription in resistant cells. Immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, RNA sequencing, in vitro and in vivo functional assays Cancer science Medium 38115797
2024 ZFP64 is identified as the transcription factor for TUBB3, directly activating the TUBB3 promoter. LncRNA FIRRE binds ZFP64 and enhances ZFP64-mediated activation of the TUBB3 promoter. Reducing ZFP64 disrupts FIRRE's positive regulation of TUBB3 in vitro and in vivo, establishing a FIRRE/ZFP64/TUBB3 axis in gastric cancer progression. Dual luciferase reporter assay (TUBB3 promoter), RIP (FIRRE-ZFP64), ChIP (ZFP64 at TUBB3 promoter), ZFP64 knockdown with TUBB3 expression readout Cancer letters Medium 39706253
2008 TUBB3 expression in ovarian cancer cells is regulated by epigenetic mechanisms: a CpG island within intron 1 is hypermethylated in one low-expressing cell line (JHOC-8), and demethylation with 5-aza-2'-deoxycytidine restores TUBB3 expression in this line. In another low-expressing cell line (OVCAR-3) with hypomethylated CpG island, TUBB3 expression is instead induced by histone deacetylase inhibition (PBA), indicating chromatin acetylation as a second epigenetic control mechanism. Demethylating agent (5-Aza-CdR) treatment, HDAC inhibitor (PBA) treatment, methylation-specific PCR of CpG island in TUBB3 intron 1, Western blot for TUBB3 protein International journal of oncology Medium 18497984
2023 A shikonin derivative (PMMB276) was identified as a direct binding partner of TUBB3 using iTRAQ proteomics and co-immunoprecipitation. PMMB276 regulates microtubule dynamics by inducing microtubule depolymerization through TUBB3, acting as a tubulin stabilizer via a mechanism distinct from paclitaxel. TUBB3 suppression or inhibition with PMMB276 reduces breast cancer growth in vivo. iTRAQ proteomics, co-immunoprecipitation, siRNA knockdown, immunofluorescence of microtubule dynamics, in vivo tumor model Phytomedicine Medium 38377719
2017 TUBB3 overexpression alone has a very minor effect on taxol sensitivity in cultured cell lines. In a taxol-resistant RPE cell line with elevated TUBB3, simultaneous P-glycoprotein (P-gP) upregulation—not TUBB3—is responsible for resistance. CRISPRa-driven robust TUBB3 overexpression from its endogenous locus results in only a minimal decrease in taxol sensitivity; selective TUBB3 depletion in high-TUBB3 breast cancer cell lines had minimal or no effect on taxol sensitivity. CRISPRa endogenous locus overexpression, taxol-resistant cell line generation, siRNA knockdown, drug sensitivity assays, P-gP functional analysis Oncotarget Medium 29069726
2022 Paracetamol (APAP) exposure in human NT2N and chicken cerebellar granule neuron models causes concentration- and time-dependent disruption of TUBB3 integrity, manifesting as increased punctate aggregation of β3-tubulin, alongside reduction in neurite arborization. This establishes a direct perturbation of TUBB3 protein organization as a mechanism of APAP neurotoxicity in vitro. Immunofluorescence of TUBB3 aggregation in two in vitro neuron models (human NT2N and chicken CGN), quantitative neurite arborization analysis Toxicology and applied pharmacology Low 35714712

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 478 20074521
2019 LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization. Cell death & disease 289 31685807
2010 Mutations in the neuronal ß-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects. Human molecular genetics 225 20829227
2018 Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is Essential for Timely Axon Regeneration. Cell reports 145 30110642
1999 CFEOM3: a new extraocular congenital fibrosis syndrome that maps to 16q24.2-q24.3. Investigative ophthalmology & visual science 85 10393037
2014 TUBB3/βIII-tubulin acts through the PTEN/AKT signaling axis to promote tumorigenesis and anoikis resistance in non-small cell lung cancer. Cancer research 83 25414139
2004 Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3). Investigative ophthalmology & visual science 74 15223798
2014 Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy. Cancer chemotherapy and pharmacology 51 25107571
2013 Direct binding of TUBB3 with DCC couples netrin-1 signaling to intracellular microtubule dynamics in axon outgrowth and guidance. Journal of cell science 51 23641072
2007 Looking at drug resistance mechanisms for microtubule interacting drugs: does TUBB3 work? Current cancer drug targets 51 18220531
2019 Targeting the IL-1β/EHD1/TUBB3 axis overcomes resistance to EGFR-TKI in NSCLC. Oncogene 47 31740781
2011 Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse and rat Sertoli cells. Biology of reproduction 47 21734264
2008 Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. International journal of oncology 47 18497984
2019 TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer. International journal of molecular sciences 45 31412591
2010 Evidence of an asymmetrical endophenotype in congenital fibrosis of extraocular muscles type 3 resulting from TUBB3 mutations. Investigative ophthalmology & visual science 45 20393110
2017 Prevalence of βIII-tubulin (TUBB3) expression in human normal tissues and cancers. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 44 29022485
2011 RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRCA1, TUBB3 and RRM1 in NSCLC. Lung cancer (Amsterdam, Netherlands) 42 21996087
2020 Exosomal miR-200c suppresses chemoresistance of docetaxel in tongue squamous cell carcinoma by suppressing TUBB3 and PPP2R1B. Aging 41 32310826
2019 ALDH1A1 in patient-derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression. International journal of cancer 40 31187490
2021 Multi-component bioresponsive nanoparticles for synchronous delivery of docetaxel and TUBB3 siRNA to lung cancer cells. Nanoscale 39 34160534
2017 Uncoupling of UNC5C with Polymerized TUBB3 in Microtubules Mediates Netrin-1 Repulsion. The Journal of neuroscience : the official journal of the Society for Neuroscience 39 28483977
2015 Tissue-specific control of midbody microtubule stability by Citron kinase through modulation of TUBB3 phosphorylation. Cell death and differentiation 39 26586574
2013 Altered TUBB3 expression contributes to the epothilone response of mitotic cells. British journal of cancer 39 23321512
2016 Multiplicity of acquired cross-resistance in paclitaxel-resistant cancer cells is associated with feedback control of TUBB3 via FOXO3a-mediated ABCB1 regulation. Oncotarget 33 27284014
2016 Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance. Cancer chemotherapy and pharmacology 32 26842788
2011 Class III β-tubulin (TUBB3): more than a biomarker in solid tumors? Current molecular medicine 32 21999149
2020 miR-200b-3p mitigates oxaliplatin resistance via targeting TUBB3 in colorectal cancer. The journal of gene medicine 26 32092782
2015 Coordinated interaction of Down syndrome cell adhesion molecule and deleted in colorectal cancer with dynamic TUBB3 mediates Netrin-1-induced axon branching. Neuroscience 25 25754961
2017 Suppression of PTEN/AKT signaling decreases the expression of TUBB3 and TOP2A with subsequent inhibition of cell growth and induction of apoptosis in human breast cancer MCF-7 cells via ATP and caspase-3 signaling pathways. Oncology reports 24 28075472
2014 Expression of ERCC1, TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal squamous cell carcinoma: A hierarchical clustering analysis. Experimental and therapeutic medicine 24 24926347
2023 TUBB3 and KIF21A in neurodevelopment and disease. Frontiers in neuroscience 23 37600020
2016 A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia. American journal of medical genetics. Part A 22 26739025
2012 Clinical implications of REST and TUBB3 in ovarian cancer and its relationship to paclitaxel resistance. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 22684772
2012 Serum levels of TUBB3 correlate with clinical outcome in Chinese patients with advanced gastric cancer receiving first-line paclitaxel plus capecitabine. Medical oncology (Northwood, London, England) 22 22766748
2018 Human TUBB3 Mutations Disrupt Netrin Attractive Signaling. Neuroscience 21 29382549
2017 An exome sequencing study of Moebius syndrome including atypical cases reveals an individual with CFEOM3A and a TUBB3 mutation. Cold Spring Harbor molecular case studies 21 28299356
2010 Alpha-MSH regulates intergenic splicing of MC1R and TUBB3 in human melanocytes. Nucleic acids research 21 21071418
2015 Expanding the phenotypic spectrum and variability of endocrine abnormalities associated with TUBB3 E410K syndrome. The Journal of clinical endocrinology and metabolism 20 25559402
2014 Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy. Molecular medicine reports 19 25573098
2024 Targeting TUBB3 Suppresses Anoikis Resistance and Bone Metastasis in Prostate Cancer. Advanced healthcare materials 18 38809199
2021 Exosomal TUBB3 mRNA expression of metastatic castration-resistant prostate cancer patients: Association with patient outcome under abiraterone. Cancer medicine 18 34318630
2020 Autosomal dominant TUBB3-related syndrome: Fetal, radiologic, clinical and morphological features. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 17 32169460
2015 Tubb3 regulation by the Erk and Akt signaling pathways: a mechanism involved in the effect of arginine ADP-ribosyltransferase 1 (Art1) on apoptosis of colon carcinoma CT26 cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 17 26373733
2014 A family with axonal sensorimotor polyneuropathy with TUBB3 mutation. Molecular medicine reports 17 25482575
2023 NOTCH3 promotes docetaxel resistance of prostate cancer cells through regulating TUBB3 and MAPK signaling pathway. Cancer science 16 38115797
2022 Long non-coding ROR promotes the progression of papillary thyroid carcinoma through regulation of the TESC/ALDH1A1/TUBB3/PTEN axis. Cell death & disease 16 35173149
2017 Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer. BMC gastroenterology 16 28056823
2013 mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in postoperative patients with non-small cell lung cancer. Asian Pacific journal of cancer prevention : APJCP 15 23803067
2010 Immunohistochemical study of HER2 and TUBB3 proteins in extramammary Paget disease. The American Journal of dermatopathology 15 20534991
2020 TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations. American journal of medical genetics. Part A 14 32573066
2020 Individualized chemotherapy guided by the expression of ERCC1, RRM1, TUBB3, TYMS and TOP2A genes versus classic chemotherapy in the treatment of breast cancer: A comparative effectiveness study. Oncology letters 14 33240427
2019 Congenital monocular elevation deficiency associated with a novel TUBB3 gene variant. The British journal of ophthalmology 14 31302631
2017 TUBB3 overexpression has a negligible effect on the sensitivity to taxol in cultured cell lines. Oncotarget 14 29069726
2015 Functional Characterization of MC1R-TUBB3 Intergenic Splice Variants of the Human Melanocortin 1 Receptor. PloS one 14 26657157
2021 The combination therapy of targeting both paclitaxel and Dendrophthoe pentandra leaves extract nanoparticles for improvement breast cancer treatment efficacy by reducing TUBB3 and MAP4 expressions. Acta biochimica Polonica 13 34264566
2023 OSGIN1 is a novel TUBB3 regulator that promotes tumor progression and gefitinib resistance in non-small cell lung cancer. Cellular and molecular life sciences : CMLS 12 37646890
2019 RILPL2 regulates breast cancer proliferation, metastasis, and chemoresistance via the TUBB3/PTEN pathway. American journal of cancer research 12 31497344
2016 A Mutation in the Tubulin-Encoding TUBB3 Gene Causes Complex Cortical Malformations and Unilateral Hypohidrosis. Child neurology open 12 28503613
2021 TUBB3 is associated with PTEN, neuroendocrine differentiation, and castration resistance in prostate cancer. Urologic oncology 10 33771409
2021 TUBB3 Promotes Growth and Invasion of Gallbladder Cancer Cells by Akt/mTOR Signal Pathway. Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 10 33822514
2021 TUBB3 M323V Syndrome Presents with Infantile Nystagmus. Genes 10 33921132
2019 Disease-associated mutations in human TUBB3 disturb netrin repulsive signaling. PloS one 10 31226147
2015 Expression of ERCC1 and TUBB3 in locally advanced cervical squamous cell cancer and its correlation with different therapeutic regimens. The International journal of biological markers 10 26165688
2014 Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy. Asian Pacific journal of cancer prevention : APJCP 10 24935362
2022 SRC Kinase-Mediated Tyrosine Phosphorylation of TUBB3 Regulates Its Stability and Mitotic Spindle Dynamics in Prostate Cancer Cells. Pharmaceutics 9 35631517
2017 Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer. International journal of molecular medicine 9 28949378
2022 Paracetamol perturbs neuronal arborization and disrupts the cytoskeletal proteins SPTBN1 and TUBB3 in both human and chicken in vitro models. Toxicology and applied pharmacology 8 35714712
2020 Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S. Tumori 8 32522106
2017 TUBB3 E410K syndrome with osteoporosis and cough syncope in a patient previously diagnosed with atypical Moebius syndrome. Brain & development 8 29289389
2023 Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology. Pathology international 7 37589430
2015 Monozygotic twins with a de novo 0.32 Mb 16q24.3 deletion, including TUBB3 presenting with developmental delay and mild facial dysmorphism but without overt brain malformation. American journal of medical genetics. Part A 7 26109418
2013 [Effect of TUBB3, TS and ERCC1 mRNA expression on chemoresponse and clinical outcome of advanced gastric cancer by multiplex branched-DNA liquid chip technology]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 7 23828702
2024 Identification of TUBB3 as an immunotherapy target in lung cancer by genome wide in vivo CRISPR screening. Neoplasia (New York, N.Y.) 6 39671912
2021 A Novel De Novo TUBB3 Variant Causing Developmental Delay, Epilepsy and Mild Ophthalmological Symptoms in a Chinese Child. Journal of molecular neuroscience : MN 6 34562182
2017 Postmortem Diagnostic Exome Sequencing Identifies a De Novo TUBB3 Alteration in a Newborn With Prenatally Diagnosed Hydrocephalus and Suspected Walker-Warburg Syndrome. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 6 29187032
2012 [The mRNA expression of BRCA1, ERCC1, TUBB3, PRR13 genes and their relationship with clinical chemosensitivity in primary epithelial ovarian cancer]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 6 22780973
2015 Expression of TS, RRM1, ERCC1, TUBB3 and STMN1 Genes in Tissues of Non-small Cell Lung Cancer and its Significance in Guiding Postoperative Adjuvant Chemotherapy. Asian Pacific journal of cancer prevention : APJCP 5 25921119
2023 A modified natural small molecule inhibits triple-negative breast cancer growth by interacting with Tubb3. Phytomedicine : international journal of phytotherapy and phytopharmacology 4 38377719
2022 TUBB3 immunostaining improves the diagnostic accuracy of oral liquid-based cytology in squamous cell carcinoma. Cytopathology : official journal of the British Society for Clinical Cytology 4 34995373
2022 Infantile esotropia in a family with TUBB3 mutation associated congenital fibrosis of extraocular muscles. Ophthalmic genetics 4 35765833
2020 Second trimester fetal MRI features in a fetus with TUBB3 gene mutation. Radiology case reports 4 33318778
2015 EGFR and K-RAS mutations and ERCC1, TUBB3, TYMS, RRM1 and EGFR mRNA expression in non-small cell lung cancer: Correlation with clinical response to gefitinib or chemotherapy. Molecular and clinical oncology 4 26623063
2024 LncRNA FIRRE drives gastric cancer progression via ZFP64-mediated TUBB3 promoter activation. Cancer letters 3 39706253
2021 Genome-wide variant calling in reanalysis of exome sequencing data uncovered a pathogenic TUBB3 variant. European journal of medical genetics 3 34863918
2020 A Complex Cortical Malformation Caused by a Mutation in the Tubulin-Encoding TUBB3 Gene. Taehan Yongsang Uihakhoe chi 3 36238036
2013 Longitudinal assessment of TUBB3 expression in non-small cell lung cancer patients. Cancer chemotherapy and pharmacology 3 24220933
2025 HOMER3 drives oral squamous cell carcinoma progression through TRPV6 calcium influx and TUBB3 microtubule stabilization. Oncogene 2 41326663
2022 Silencing TUBB3 Expression Destroys the Tegument and Flame Cells of Echinococcus multilocularis Protoscoleces. Animals : an open access journal from MDPI 2 36139331
2020 Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer. Clinical breast cancer 2 33008754
2015 [Expressions of TUBB3 and γ-synuclein in colorectal adenocarcinoma and their clinical significance]. Zhonghua yi xue za zhi 2 26081510
2014 Joint detection of ERCC1, TUBB3, and TYMS guidance selection of docetaxel, 5-fluorouracil and cisplatin (DDP) individual chemotherapy in advanced gastric cancer patients. European journal of medical research 2 25223338
2013 [Correlation between expression of TUBB3/STMN1 and EGFR signaling pathway in non-small cell lung cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 2 24113009
2013 Lack of expression of TUBB3 characterizes both BCL2-positive and BCL2-negative follicular lymphoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2 24232867
2025 KIF21A-associated peripheral neuropathy defined by impaired binding with TUBB3. Journal of medical genetics 1 39643435
2023 Establishment of TUBB3-mCherry knock-in human pluripotent stem cell line using CRISPR/Cas9 (SNUe003-A-4). Stem cell research 1 36913849
2023 Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells. Biomolecules & therapeutics 1 38072501
2015 [TUBB3 role in the response of tumor cells to epothilones and taxanes]. Postepy higieny i medycyny doswiadczalnej (Online) 1 25661915
2012 [Molecular cloning of tubulin beta 3 (TUBB3) in Gekko japonicus and preparation of its polyclonal antibody]. Dong wu xue yan jiu = Zoological research 1 22855447
2024 NF1 mutation and TUBB3 amplification in gastric histiocytic sarcoma: a case report and literature review. Medical molecular morphology 0 38914690
2022 TUBB3 E410K Syndrome With Childhood-Onset Nonalcoholic Steatohepatitis. The Journal of clinical endocrinology and metabolism 0 34435630

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