Affinage

Showing TRIM33 — PTC7 is a alias.

TRIM33

E3 ubiquitin-protein ligase TRIM33 · UniProt Q9UPN9

Length
1127 aa
Mass
122.5 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRIM33 (TIF1γ) is a multidomain nuclear factor that integrates TGFβ/Nodal/BMP signaling with chromatin regulation to control cell fate decisions, hematopoiesis, and tumor suppression (PMID:16751102, PMID:20573697). It establishes a distinct branch of TGFβ signaling by selectively binding receptor-phosphorylated Smad2/3 in competition with Smad4, routing the pathway toward differentiation rather than the antiproliferative response (PMID:16751102), and acts in vivo as a Smad4 inhibitor that limits Nodal responsiveness during embryonic patterning (PMID:20573697). Architecturally TRIM33 carries RING, B-box, coiled-coil, PHD finger, and bromodomain motifs and possesses intrinsic transcriptional silencing activity (PMID:10022127); its PHD finger–bromodomain forms a multivalent histone-binding module that reads H3 tails unmethylated at K4/R2 and acetylated at key lysines, and this histone engagement licenses its E3 ubiquitin ligase activity toward Smad4 and its repressive output (PMID:21726812). The bromodomain uniquely recognizes histone lysine lactylation through a distinguishing glutamate in its binding pocket (PMID:39556662). Beyond chromatin reading, TRIM33 promotes transcription elongation of lineage-specific genes by partnering with the SCL/TAL1 complex and the elongation factors p-TEFb and FACT to relieve RNA Pol II pausing (PMID:20603019, PMID:21474105), a function extended to coenzyme Q biosynthesis genes whose loss perturbs erythroid differentiation through metabolite-driven histone hypermethylation (PMID:33986176). As an E3 ubiquitin ligase TRIM33 targets a range of substrates—including HIV-1 integrase to restrict infection (PMID:30804369), TFRC to promote ferroptosis (PMID:38909931), p53 to de-repress glycolysis (PMID:39389957), and E2F4 to govern replication fork integrity via Recql recruitment under stress (PMID:37612308)—and acts as a SUMO E3 ligase for SnoN1 to suppress TGFβ-driven EMT (PMID:25059663). It forms regulatory complexes with TRIM24 and TRIM28 that suppress hepatocellular carcinoma (PMID:21531907) and operates as a tumor suppressor in pancreas independent of Smad4 (PMID:19629168, PMID:22469842). In immune cells, TRIM33 is recruited by PU.1 to specific enhancers to repress Ifnb1, Bim, and other targets, tuning macrophage, dendritic cell, and lymphocyte programs (PMID:26592194, PMID:25919951, PMID:38822080).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1999 High

    Established the domain architecture and intrinsic activity of TIF1γ, distinguishing it from other TIF1 family members.

    Evidence Yeast two-hybrid, GST pull-down, reporter assays and deletion mutagenesis defining RING/B-box/coiled-coil/PHD/bromodomain motifs and a TIF1 signature sequence

    PMID:10022127

    Open questions at the time
    • No physiological substrate or chromatin target identified at this stage
    • Functional consequence of silencing activity in vivo unknown
  2. 2006 High

    Defined TIF1γ as a competitor of Smad4 for phospho-Smad2/3, creating a branch point that directs TGFβ signaling toward differentiation.

    Evidence Co-IP and loss-of-function in human hematopoietic stem/progenitor cells with differentiation readouts

    PMID:16751102

    Open questions at the time
    • Molecular basis of selective Smad2/3 recognition not structurally resolved
    • Whether competition is regulated post-translationally not addressed
  3. 2010 High

    Resolved how TIF1γ activates lineage genes mechanistically and how it acts as an in vivo Smad4 inhibitor in embryos.

    Evidence Zebrafish moonshine genetic epistasis with elongation factors plus Co-IP/ChIP; conditional Nodal-pathway ablation in mouse embryos

    PMID:20573697 PMID:20603019

    Open questions at the time
    • How elongation-promoting and Smad4-inhibitory functions are coordinated unclear
    • Direct recruitment mechanism to elongation machinery not fully defined
  4. 2011 High

    Connected chromatin reading to enzymatic output and placed TRIM33 in tumor-suppressive multi-TRIM complexes and hematopoietic TF complexes.

    Evidence In vitro histone binding, ligase and reporter assays (Mol Cell); MS co-purification with conditional KO mice (PNAS); Co-IP/ChIP with TAL1/PU.1 and conditional KO (Cell Stem Cell)

    PMID:21474105 PMID:21531907 PMID:21726812

    Open questions at the time
    • Stoichiometry and assembly of TRIM24/28/33 complexes unresolved
    • How histone marks toggle ligase activity structurally undefined
  5. 2013 Medium

    Extended TRIM33 function to DNA damage response and post-translational control of its own repressive activity by SUMOylation.

    Evidence Proteomics, live imaging and PARP1/ALC1 epistasis (JBC); SUMO-site mutagenesis with ChIP/reporter assays (J Cell Sci)

    PMID:23788427 PMID:23926104

    Open questions at the time
    • Whether TRIM33 ubiquitylates ALC1 at this stage not shown
    • Link between SUMOylation and chromatin recruitment incomplete
  6. 2015 High

    Diversified TRIM33's substrate repertoire and enhancer-targeted repression, identifying β-catenin ubiquitylation, PU.1-directed Bim repression, Ifnb1 control, and a chromosomal-stability role.

    Evidence Ubiquitylation/Co-IP with kinase mutants (Nat Commun); ChIP-seq with CRISPR enhancer deletion (eLife); ChIP-seq/conditional KO in macrophages (Nat Commun); mitotic checkpoint assays (Cancer Res)

    PMID:25639486 PMID:25919951 PMID:26282171 PMID:26592194

    Open questions at the time
    • Generalizability of β-catenin ubiquitylation across cell types untested (later contradicted in mESCs)
    • How PU.1 recruits TRIM33 to specific enhancers undefined
  7. 2015 High

    Established SUMO ligase activity toward SnoN1 and a testis-specific role silencing endogenous retroviruses via A-MYB ubiquitylation.

    Evidence In vitro SUMO ligase and organoid EMT assays (JBC); ChIP-seq, RNA-seq and A-MYB ubiquitination in testis (PLoS Genet)

    PMID:25059663 PMID:26624618

    Open questions at the time
    • Isoform selectivity determinants for SnoN1 vs SnoN2 only partly mapped
    • In vivo consequence of ERV de-silencing on fertility not fully quantified
  8. 2017 Medium

    Broadened TRIM33's signaling reach to BMP-driven osteoblast differentiation, PML-body localization in stem cells, and myeloid cell motility.

    Evidence Co-IP/phospho-Smad1/5 assays in osteoblast lines; zebrafish imaging and 3D motility assays in macrophages

    PMID:28063228 PMID:28724755

    Open questions at the time
    • Mechanism of Smad1/5 phosphorylation promotion by TRIM33 unclear
    • Molecular driver of amoeboid motility defect not identified
  9. 2019 High

    Showed TRIM33 RING-ligase activity restricts viral integration and contributes negatively to fibrotic and Th17/Treg-type immune programs.

    Evidence RNAi screen with HIV-1 replication and IN-mutant epistasis (Nat Commun); conditional T-cell KO with ChIP and autoimmune model (JEM)

    PMID:29930104 PMID:30804369

    Open questions at the time
    • Direct ubiquitin transfer to integrase not biochemically reconstituted
    • How Smad2-dependent recruitment to Il17a/Il10 loci occurs unresolved
  10. 2022 High

    Linked TRIM33 transcription-elongation control to coenzyme Q metabolism and detailed FACT-dependent enhancer regulation and PML-body co-regulation of Nodal targets.

    Evidence Chemical suppressor screen with metabolic profiling and CoQ rescue (Science); ChIP-seq/Co-IP with SPT16 (Epigenetics Chromatin); TurboID and PML-KO epistasis (EMBO J)

    PMID:31331374 PMID:33986176 PMID:36524443

    Open questions at the time
    • Direct vs indirect control of CoQ genes via metabolite feedback hard to separate
    • Cell-type specificity of PML-body recruitment mechanism undefined
  11. 2023 High

    Established E2F4/Recql-dependent control of replication fork integrity and identified upstream regulators (TRIM21, YOD1) governing TRIM33 stability.

    Evidence E2F4 ubiquitination, Co-IP, ChIP-seq and DNA fiber assays with conditional KO (Nat Commun); MS/Co-IP/ubiquitin-site mapping (Theranostics, Cell Death Dis)

    PMID:37573347 PMID:37612308 PMID:37771771

    Open questions at the time
    • How replicative stress blunts E2F4 ubiquitylation mechanistically unclear
    • Interplay of TRIM21 degradation and YOD1 stabilization not jointly studied
  12. 2024 Medium

    Defined the bromodomain's unique lactyl-lysine recognition and expanded substrate/target roles across p53-glycolysis, AR transcription, NHEJ, and dendritic-cell programs.

    Evidence ITC/NMR/mutagenesis bromodomain screen (ACS Chem Biol); K48-ubiquitination of p53 (Cell Death Dis); ChIP-seq/H2BK120ub (Commun Biol); ALC1-ubiquitination NHEJ assays (Sci Rep); conditional KO with ChIP at Irf8/Bcl2l11 (CMI)

    PMID:38627415 PMID:38822080 PMID:39389957 PMID:39556662 PMID:40646276

    Open questions at the time
    • Whether TRIM33 affects AR protein stability remains contradictory across studies (#23 vs #24)
    • Physiological writers/erasers of the lactyl mark read by TRIM33 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRIM33's many enzymatic activities (ubiquitin and SUMO ligase) and chromatin-reading functions are selectively deployed across cell types and substrates remains the central open question.
  • No unifying structural model linking histone-mark recognition to substrate choice
  • Determinants of context-specific substrate selection (β-catenin, p53, TFRC, E2F4, AR) undefined
  • Cell-type-specific contradictory phenotypes (e.g. β-catenin, AR) unreconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 6 GO:0140096 catalytic activity, acting on a protein 6 GO:0140110 transcription regulator activity 4 GO:0003677 DNA binding 2 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3
Partners
PU.1SMAD2/3SMAD4SPT16TAL1TRIM21TRIM24TRIM28
Complex memberships
PIAS1-TIF1γ-SnoN SUMOylation complexSCL/TAL1 complexTRIM24/TRIM28/TRIM33 complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 TIF1γ selectively binds receptor-phosphorylated Smad2/3 in competition with Smad4, forming a distinct branch of the TGFβ pathway. In hematopoietic cells, Smad2/3-TIF1γ mediates erythroid differentiation while Smad2/3-Smad4 mediates the antiproliferative response. Co-immunoprecipitation, cell-based TGFβ signaling assays, loss-of-function in human hematopoietic stem/progenitor cells Cell High 16751102
1999 TIF1γ contains RING finger, B-box, coiled-coil, PHD/TTC, and bromodomain structural motifs. Unlike TIF1α, it does not interact with nuclear receptors or HP1 proteins, but exhibits transcriptional silencing activity dependent on a novel TIF1 signature sequence (TSS). Yeast two-hybrid, GST pull-down, transfection-based reporter assays, deletion mutagenesis Oncogene High 10022127
2010 TIF1γ promotes transcription elongation of erythroid genes by physically interacting with the SCL transcription complex and positive elongation factors p-TEFb and FACT, counteracting RNA Pol II pausing. Loss of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1γ-deficient zebrafish. Genetic epistasis in zebrafish moonshine mutants, biochemical co-immunoprecipitation, chromatin immunoprecipitation (ChIP) in human CD34+ cells Cell High 20603019
2011 The PHD finger-bromodomain of TIF1γ constitutes a multivalent histone-binding module that specifically binds histone H3 tails unmethylated at K4 and R2 and acetylated at key lysines. Histone binding by this module is required for TIF1γ's E3 ubiquitin ligase activity toward Smad4 and its transcriptional repressor activity; histone binding induces the E3 ligase activity. In vitro histone-binding assays, mutagenesis of PHD finger-bromodomain, ubiquitin ligase assays, transcriptional reporter assays Molecular Cell High 21726812
2011 TRIM33 forms macromolecular complexes with TRIM24 and TRIM28 in hepatocytes. Somatic hepatocyte-specific inactivation of any of the three proteins promotes hepatocellular carcinoma in a cell-autonomous manner, and TRIM33 loss potentiates HCC formation upon TRIM24 inactivation. Protein purification and mass spectrometry (co-purification), conditional knockout mouse models, genetic interaction studies PNAS High 21531907
2015 TRIM33 acts as an E3 ubiquitin ligase that ubiquitylates nuclear β-catenin, promoting its proteasomal degradation in a GSK-3β- and β-TrCP-independent manner. PKCδ-mediated phosphorylation of β-catenin at Ser715 is required for the TRIM33-β-catenin interaction. Co-immunoprecipitation, ubiquitylation assays, rescue experiments with kinase inhibitors/mutants, in vivo tumor models Nature Communications High 25639486
2013 TRIM33 is dynamically recruited to DNA damage sites in a PARP1- and ALC1-dependent manner. TRIM33 interacts with the chromatin-remodeling enzyme ALC1 after DNA damage and promotes its timely removal from DNA break sites; TRIM33-deficient cells show enhanced sensitivity to DNA damage and prolonged ALC1 retention. Proteomic analysis, live-cell imaging of TRIM33 recruitment, PARP inhibitor and ALC1 knockdown epistasis, DNA damage sensitivity assays Journal of Biological Chemistry Medium 23926104
2015 TRIM33 is recruited by PU.1 to a conserved 15 kb upstream region (ICE) of the Ifnb1 gene in macrophages. At late phases of LPS activation, TRIM33 bound to ICE controls Ifnb1 enhanceosome loading and represses Ifnb1 transcription by preventing CBP/p300 recruitment. ChIP-seq, conditional Trim33 knockout in macrophages, chromatin conformation (loop analysis), luciferase/reporter assays Nature Communications High 26592194
2011 TIF1γ forms complexes with TAL1 and PU.1 in adult hematopoietic cells, occupies specific subsets of their DNA binding sites in vivo, and represses their transcriptional activity, thereby regulating adult hematopoiesis. Co-immunoprecipitation, ChIP in hematopoietic cells, conditional knockout mouse model with transplantation assays Cell Stem Cell High 21474105
2014 TIF1γ operates as a SUMO E3 ligase for SnoN1 (but not the isoform SnoN2), promoting SnoN1 sumoylation at distinct lysine residues. This sumoylation is required for SnoN1 to suppress TGFβ-induced EMT in mammary epithelial organoids. A 16-amino acid region unique to SnoN1 mediates the TIF1γ interaction. Interaction proteomics, in vitro SUMO E3 ligase assay, site-directed mutagenesis, 3D organoid EMT model Journal of Biological Chemistry High 25059663
2013 TIF1γ requires sumoylation at four sites within its middle (Smad interaction) domain by Ubc9 for its repressive activity on TGFβ signaling. A sumoylation-defective TIF1γ mutant shows reduced inhibition of Smad complexes and impaired limitation of Smad4 binding at the PAI-1 TGFβ target gene promoter. Co-immunoprecipitation with Ubc9, SUMO site mutagenesis, chromatin immunoprecipitation, TGFβ reporter assays, EMT assays Journal of Cell Science High 23788427
2019 TRIM33 functions as an E3 RING ligase that targets HIV-1 integrase (IN) for proteasomal degradation, restricting HIV-1 infection and proviral DNA formation. TRIM33 knockdown increases HIV-1 replication, while overexpression decreases it; knockdown reverts the phenotype of an IN S57A mutation known to impair integration. RNAi screen against ubiquitin-conjugation machinery, high-content microscopy, overexpression/knockdown with HIV-1 replication assays, genetic epistasis with IN mutant Nature Communications High 30804369
2018 Trim33 is recruited to the Il17a and Il10 gene loci in a Smad2-dependent manner and mediates chromatin remodeling at these loci during Th17 differentiation. Trim33 promotes IL-17 expression and suppresses IL-10 expression, contrasting with Smad4 whose loss enhanced IL-10 production. Conditional T cell-specific Trim33 knockout, ChIP at Il17a and Il10 loci, in vitro Th17 differentiation assays, in vivo autoimmune disease model Journal of Experimental Medicine High 29930104
2016 Adenovirus E4-ORF3 acts as a SUMO E3 ligase for TIF1γ in vitro, directly stimulating its sumoylation and poly-SUMO3 chain formation. E4-ORF3 multimerization is required for these activities; E4-ORF3 facilitates both initial SUMO3 conjugation to TIF1γ and chain elongation. In vitro sumoylation reconstitution with purified E4-ORF3, TIF1γ substrate assays, SUMO chain elongation assays, E4-ORF3 multimerization mutants PNAS High 27247387
2018 Nuclear c-Abl tyrosine kinase phosphorylates TIF1γ at Tyr-524, -610, and -1048. Replacing these three tyrosines with phenylalanine (3YF) enhances TIF1γ association with Smad3 and strengthens TIF1γ-mediated suppression of TGFβ signaling. EGF-activated c-Abl phosphorylates TIF1γ to desuppress TGFβ/Smad2/3 signaling and synergize with TGFβ in EMT induction. Tyrosine phosphorylation mapping, site-directed mutagenesis (3YF), knockdown-rescue experiments, Co-IP, TGFβ signaling reporter assays, EMT assays Oncogene Medium 30177833
2014 Tif1γ controls TGF-β1 receptor (Tgfbr1) turnover in hematopoietic stem cells, regulating their sensitivity to TGFβ signaling and the balance between myeloid-biased and myeloid-lymphoid-balanced HSC populations. Tif1γ-deficient HSCs phenocopy accelerated aging. Conditional Tif1γ knockout in HSCs, Tgfbr1 receptor turnover assays, flow cytometric analysis of HSC populations, comparison with aged wild-type HSCs PNAS Medium 25002492
2010 Ectodermin/Trim33 functions as a Smad4 inhibitor in vivo that limits Nodal responsiveness in mammalian embryos. Genetic ablation of Ecto leads to excessive Nodal activity affecting anterior visceral endoderm Nodal antagonist expression, trophoblast Nodal-dependent stem cell/differentiation balance, and epiblast mesoderm fate allocation. Conditional and ubiquitous genetic ablation (Cre/loxP), epistasis with Nodal signaling pathway, phenotypic analysis of multiple embryonic territories Development High 20573697
2009 Tif1γ inactivation cooperates with oncogenic KrasG12D to induce cystic pancreatic tumors (IPMNs) in mice, demonstrating a tumor suppressor function in the pancreas distinct from that of Smad4 (different histological features despite similar pathway context). Conditional pancreas-specific Tif1γ knockout, compound Pdx1-Cre;LSL-KrasG12D;Tif1γlox/lox mice, histological and IHC analysis PLoS Genetics High 19629168
2012 Tif1γ tumor-suppressor effects in pancreatic carcinogenesis are independent of Smad4, as shown by accelerated tumor progression in Pdx1-Cre;LSL-KrasG12D;Smad4lox/lox;Tif1γlox/lox quadruple mutant mice progressing through IPMN to PDAC. Compound conditional knockout mice (quadruple mutant), tumor progression analysis American Journal of Pathology High 22469842
2015 TIF1γ inactivation causes accumulation of chromosomal defects due to attenuation of both spindle assembly checkpoint and post-mitotic checkpoint activities, indicating TIF1γ promotes chromosomal stability. TIF1γ knockdown/knockout with mitotic checkpoint assays, chromosomal instability measurements, anchorage-independent growth assays, in vivo tumor models Cancer Research Medium 26282171
2015 TRIM33 is recruited to a PU.1-occupied enhancer upstream of the pro-apoptotic gene Bim in B cell leukemia, where it antagonizes PU.1-mediated Bim activation. Deletion of this single enhancer element renders TRIM33 dispensable for leukemia cell survival. ChIP-seq, conditional TRIM33 deletion, CRISPR/Cas9 enhancer deletion, PU.1 co-occupancy analysis eLife High 25919951
2020 HSPB5 (crystallin alpha B) directly binds TRIM33, reduces its protein level, and impairs the TRIM33/SMAD4 interaction. Loss of TRIM33 in macrophages increases TGFβ1 secretion and sensitizes to BLM-induced fibrosis; TRIM33 acts as a negative regulator of lung fibrosis through the TGFβ/SMAD pathway. Direct binding assay (in vitro pull-down), co-immunoprecipitation of TRIM33/HSPB5, conditional Trim33 knockout in hematopoietic cells and lung fibroblasts, 3D lung tissue slice ex vivo European Respiratory Journal Medium 32184320
2021 TIF1γ directly controls the transcription of coenzyme Q (CoQ) biosynthesis genes through transcription elongation. Loss of tif1γ reduces CoQ levels, elevates the succinate/α-ketoglutarate ratio, and leads to increased histone methylation, impairing erythroid differentiation. DHODH inhibition or CoQ analog treatment rescues the bloodless phenotype. Chemical suppressor screen in zebrafish moonshine mutants, metabolic profiling (CoQ levels, succinate/α-KG ratio), ChIP, CoQ analog rescue Science High 33986176
2022 TRIM33 facilitates androgen receptor (AR) chromatin binding and transcriptional output in prostate cancer cells, and protects AR from Skp2-mediated ubiquitination and proteasomal degradation. TRIM33 knockdown sensitizes prostate cancer cells to AR antagonists. Proteomics (AR-interactor identification), ChIP-seq, co-immunoprecipitation, ubiquitination assays, knockdown with proliferation/apoptosis readouts EMBO Reports Medium 35785414
2025 TRIM33 does not impact AR protein stability (contradicting a prior report), but instead facilitates maximal AR transcriptional activity by interfering with H2BK120 ubiquitination levels at AR-bound chromatin sites. ChIP-seq, AR protein stability assays, H2BK120 ubiquitination measurements, multiple prostate cancer cell lines Communications Biology Medium 40646276
2024 The TRIM33 bromodomain is the sole bromodomain (among 28 tested) that binds histone lysine lactylation (Kla) peptides with submicromolar affinity, also binding lysine acetylation. A unique glutamic acid residue in the TRIM33 bromodomain binding pocket confers selective recognition of Kla; mutagenesis of this residue abolishes selectivity. AlphaScreen bromodomain screen (28 bromodomains), isothermal titration calorimetry, NMR, site-directed mutagenesis, molecular modeling, X-ray crystallography (referenced in adjacent paper) ACS Chemical Biology High 39556662
2015 Trim33 acts as an E3 ubiquitin ligase for A-MYB, regulating its abundance in testis, and binds RLTR10B LTR elements (of MMERVK10C retrotransposons) in a pattern overlapping A-Myb binding sites, thereby silencing this class of young endogenous retroviruses. ChIP-seq in testis, RNA-seq in haploinsufficient Trim33 mice, A-MYB ubiquitination assay, transgene reporter screen PLoS Genetics Medium 26624618
2020 TRIM33 inhibits CBP-mediated FOXO3a acetylation by binding CBP, thereby attenuating FOXO3a ubiquitylation and degradation. This protects osteoblasts from oxidative stress-induced apoptosis; TRIM33 and FOXO3a co-localize in osteoblast nuclei. Co-immunoprecipitation of TRIM33/CBP, immunofluorescence co-localization, FOXO3a acetylation/ubiquitylation assays, overexpression/knockdown with apoptosis readouts, in vivo ovariectomy model Aging Cell Medium 34101965
2023 TRIM33 ubiquitin ligase targets E2F4 for degradation in unperturbed cells. Under replicative stress, TRIM33-dependent ubiquitination of E2F4 is blunted, allowing transient E2F4 stabilization and recruitment of the DNA helicase Recql to facilitate DNA replication fork progression. Chronic Trim33 deletion leads to genome-wide Recql recruitment, accelerated replication under stress, impaired checkpoint signaling and DNA repair. Co-immunoprecipitation of E2F4-Recql, E2F4 ubiquitination assays, ChIP-seq, DNA fiber assays (replication fork progression), conditional Trim33 knockout Nature Communications High 37612308
2022 TRIM33 interacts with FACT subunit SPT16 at PU.1-bound distal regulatory elements in macrophages. TRIM33 deficiency leads to FACT release, loss of positioned nucleosomes, RNA Pol II recruitment, and bidirectional transcription at these elements, resulting in increased Atp1b3 expression. ChIP-seq of TRIM33 and SPT16, Co-immunoprecipitation of TRIM33/SPT16, conditional Trim33 KO macrophages, nucleosome positioning analysis Epigenetics & Chromatin Medium 31331374
2022 TRIM33 co-localizes with PML nuclear bodies (PML-NBs) specifically in mouse embryonic stem cells (mESCs) but not other cell types, in a PML-dependent manner. TRIM33 and PML co-regulate Lefty1/2 expression downstream of Nodal signaling; PML-NB assembly is required for TRIM33 recruitment to these gene loci. Co-localization imaging (confocal), TurboID proximity labeling, PML knockout epistasis, ChIP, Nodal signaling reporter assays EMBO Journal Medium 36524443
2022 TRIM33 acts as an E3 ubiquitin ligase that ubiquitylates TFRC (transferrin receptor), targeting it for proteasomal degradation, thereby promoting ferroptosis susceptibility in hepatocellular carcinoma cells. Immunoprecipitation, immunofluorescence, ubiquitination assay of TFRC by TRIM33, ferroptosis readouts (MDA, Fe2+ levels, mitochondrial superoxide), in vivo xenograft Cellular Signalling Medium 38909931
2024 TRIM33 promotes K48-linked polyubiquitination of p53 at the K351 site, leading to its proteasomal degradation, thereby de-repressing downstream glycolytic target genes (GLUT1, HK2, PKM2, LDHA) and promoting aerobic glycolysis in esophageal squamous cell carcinoma. Co-immunoprecipitation, K48-linked ubiquitination assay, site-directed mutagenesis of p53 K351, in vitro and in vivo tumor growth assays Cell Death & Disease Medium 39389957
2023 TRIM21 forms a complex with TIF1γ/TRIM33 in the nucleus and promotes K48-linked ubiquitination of TIF1γ at K5, leading to its degradation, which increases nuclear β-catenin presence and promotes glioblastoma progression. Tandem Mass Tags/MS substrate identification, Co-IP, luciferase reporter assays, gain/loss of function with RING-finger deletion mutant, in vivo siRNA treatment Theranostics Medium 37771771
2023 YOD1 deubiquitinase stabilizes TRIM33 by suppressing its ubiquitination and degradation, thereby maintaining TRIM33-mediated inhibition of the ERK/β-catenin pathway in head and neck squamous cell carcinoma. Co-immunoprecipitation, ubiquitination assays, YOD1 knockdown/overexpression with TRIM33 stability readout, in vitro and in vivo tumor assays Cell Death & Disease Medium 37573347
2022 TRIM33 induces K63-linked ubiquitination of Annexin A2 in keratinocytes, promoting Annexin A2 interaction with p50/p65 NF-κB subunits, retaining them in the nucleus and driving expression of NF-κB downstream inflammatory genes in psoriasis. Immunoprecipitation combined with mass spectrometry (substrate identification), K63-ubiquitination assay, Co-IP of Anxa2/NF-κB, NF-κB target gene expression, overexpression/knockdown assays Journal of Dermatological Science Medium 36096861
2017 In zebrafish embryos, Trim33 is required cell-autonomously for macrophage colonization of the CNS (microglial seeding) and for basal amoeboid motility and inflammatory recruitment of both macrophages and neutrophils; mouse Trim33-deficient bone marrow-derived macrophages show strongly reduced 3D amoeboid mobility in collagen gels. Trim33-deficient zebrafish embryo imaging, 3D collagen gel motility assays with mouse Trim33 KO BMDMs, bacterial infection recruitment assay Journal of Cell Science Medium 28724755
2024 TRIM33 promotes transcription of Irf8 in DC progenitors by maintaining CDK9 and Ser2-phosphorylated RNA Pol II levels at the Irf8 gene, facilitating cDC1 differentiation. TRIM33 also directly suppresses PU.1-mediated transcription of Bcl2l11 (Bim) to prevent apoptosis of DCs and progenitors. Conditional Trim33 knockout (Trim33fl/fl Cre-ERT2), ChIP for CDK9 and Ser2-Pol II at Irf8 locus, ChIP for PU.1/TRIM33 at Bcl2l11 locus, flow cytometry of DC progenitors Cellular & Molecular Immunology Medium 38822080
2020 TRIM33 interacts with β-catenin in mESCs but its RING domain does not function as an E3 ubiquitin ligase for β-catenin in this context (neither KO nor overexpression of TRIM33 affects β-catenin protein levels in mESCs). TRIM33 regulates a subset of Wnt target genes (including Mixl1) independently of its RING domain E3 ligase activity. Co-immunoprecipitation in mESCs, Trim33 knockout and overexpression with β-catenin protein level measurements, Wnt reporter assay, Wnt target gene expression analysis Science China Life Sciences Medium 28844090
2017 TRIM33 positively regulates osteoblast differentiation through the BMP pathway by forming a TRIM33-Smad1/5 complex that triggers Smad1/5 phosphorylation. Co-immunoprecipitation of TRIM33-Smad1/5, phospho-Smad1/5 Western blotting, TRIM33 overexpression/knockdown in C3H10T1/2 and MC3T3-E1 cells with osteoblast differentiation markers Journal of Cellular Physiology Medium 28063228
2011 Adenovirus E4-ORF3 interacts with TIF1γ through its Coiled-Coil domain and relocalizes endogenous TIF1γ into nuclear track structures in infected cells. The C-terminal half of TIF1β interferes with this interaction, explaining differential targeting of TIF1 family members. Co-immunoprecipitation in vitro and in infected cells, domain mapping with TIF1 chimeras, immunofluorescence of nuclear relocalization Virology Medium 22123502
2021 TIF1γ binds TBP in competition with TAF15, impedes TAF15/TBP-mediated IL-6 transactivation, and induces multi-mono-ubiquitylation of TAF15, driving its nuclear export. This suppresses EMT and metastasis of lung adenocarcinoma cells. Co-immunoprecipitation of TIF1γ/TBP and TIF1γ/TAF15, competition assay, ubiquitylation assay of TAF15, nuclear export assay, EMT/invasion assays Cell Reports Medium 36261009
2020 PIAS1 and TIF1γ form a trimeric complex with SnoN to collaboratively promote SnoN SUMOylation. Loss-of-function studies demonstrate that PIAS1 and TIF1γ act in an interdependent (not additive) manner to suppress EMT in breast cell-derived tissue organoids. Co-immunoprecipitation of trimeric complex, SUMO ligase assays, knockdown of PIAS1 and/or TIF1γ in 3D organoid EMT model Cell Death and Differentiation Medium 32770107
2024 TRIM33 loss in multiple myeloma leads to dysregulated ubiquitination of ALC1, impaired non-homologous end joining (NHEJ), accumulation of DNA double strand breaks, and sensitization to PARP inhibitor Olaparib. This effect is synergistic with bortezomib. TRIM33 knockdown in MM cells, NHEJ efficiency assay, DNA damage (DSB) quantification, ALC1 ubiquitination assay, PARP inhibitor sensitivity assay, co-culture with bone marrow stromal cells Scientific Reports Medium 38627415
2022 In the context of sepsis, parthenolide (PA) covalently targets TRIM33 via cysteine engagement, functionally binding TRIM33 to reduce Smad4 ubiquitin-dependent degradation, thereby suppressing NF-κB pathway activation and inflammation. Streamlined cysteine ABPP (activity-based protein profiling) chemoproteomics, proteomics, Co-IP, NF-κB reporter assays, in vivo CLP sepsis model Phytomedicine Low 41702258

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell 321 16751102
2018 Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer. Molecular cancer 295 30261900
2011 Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma. Proceedings of the National Academy of Sciences of the United States of America 184 21531907
2010 TIF1gamma controls erythroid cell fate by regulating transcription elongation. Cell 178 20603019
2015 Tumour suppressor TRIM33 targets nuclear β-catenin degradation. Nature communications 150 25639486
1999 TIF1gamma, a novel member of the transcriptional intermediary factor 1 family. Oncogene 143 10022127
2011 Recruitment of TIF1γ to chromatin via its PHD finger-bromodomain activates its ubiquitin ligase and transcriptional repressor activities. Molecular cell 130 21726812
2009 Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS genetics 98 19629168
2020 TRIM33 prevents pulmonary fibrosis by impairing TGF-β1 signalling. The European respiratory journal 82 32184320
2010 Negative control of Smad activity by ectodermin/Tif1gamma patterns the mammalian embryo. Development (Cambridge, England) 77 20573697
2015 Repression of TIF1γ by SOX2 promotes TGF-β-induced epithelial-mesenchymal transition in non-small-cell lung cancer. Oncogene 73 25961934
2014 miR-629 Targets TRIM33 to Promote TGFβ/Smad Signaling and Metastatic Phenotypes in ccRCC. Molecular cancer research : MCR 70 25381221
2014 Tif1γ regulates the TGF-β1 receptor and promotes physiological aging of hematopoietic stem cells. Proceedings of the National Academy of Sciences of the United States of America 63 25002492
2011 Antagonistic regulation of EMT by TIF1γ and Smad4 in mammary epithelial cells. EMBO reports 61 21597466
2019 Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation. Nature communications 59 30804369
2013 Tripartite Motif-containing 33 (TRIM33) protein functions in the poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response through interaction with Amplified in Liver Cancer 1 (ALC1) protein. The Journal of biological chemistry 59 23926104
2015 TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation. Nature communications 58 26592194
2021 Oncocytic intraductal carcinoma of salivary glands: a distinct variant with TRIM33-RET fusions and BRAF V600E mutations. Histopathology 53 33135196
2018 Trim33 mediates the proinflammatory function of Th17 cells. The Journal of experimental medicine 51 29930104
2021 TRIM33 protects osteoblasts from oxidative stress-induced apoptosis in osteoporosis by inhibiting FOXO3a ubiquitylation and degradation. Aging cell 46 34101965
2016 Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-β-dependent mechanisms. Proceedings of the National Academy of Sciences of the United States of America 43 27432991
2012 Anti-TIF1γ antibodies (anti-p155) in adult patients with dermatomyositis: comparison of different diagnostic assays. Annals of the rheumatic diseases 43 22294626
2021 Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis. Science (New York, N.Y.) 41 33986176
2015 The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer. eLife 40 25919951
2024 The TRIM33 Bromodomain Recognizes Histone Lysine Lactylation. ACS chemical biology 38 39556662
2011 Adult hematopoiesis is regulated by TIF1γ, a repressor of TAL1 and PU.1 transcriptional activity. Cell stem cell 36 21474105
2012 TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes. Developmental biology 35 23159334
2015 TIF1γ interferes with TGFβ1/SMAD4 signaling to promote poor outcome in operable breast cancer patients. BMC cancer 33 26040677
2022 Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies. Annals of the rheumatic diseases 32 36008132
2014 TIF1γ protein regulates epithelial-mesenchymal transition by operating as a small ubiquitin-like modifier (SUMO) E3 ligase for the transcriptional regulator SnoN1. The Journal of biological chemistry 32 25059663
2014 Tak1, Smad4 and Trim33 redundantly mediate TGF-β3 signaling during palate development. Developmental biology 32 25523394
2023 E3 ubiquitin ligase TRIM21 targets TIF1γ to regulate β-catenin signaling in glioblastoma. Theranostics 31 37771771
2015 TIF1γ Suppresses Tumor Progression by Regulating Mitotic Checkpoints and Chromosomal Stability. Cancer research 31 26282171
2012 Tif1γ suppresses murine pancreatic tumoral transformation by a Smad4-independent pathway. The American journal of pathology 31 22469842
2011 Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma. World journal of gastroenterology 31 22046087
2013 TIF1γ requires sumoylation to exert its repressive activity on TGFβ signaling. Journal of cell science 30 23788427
2017 Macrophage production and activation are dependent on TRIM33. Oncotarget 28 27974684
2008 Generation of mice with a conditional allele for Trim33. Genesis (New York, N.Y. : 2000) 28 18543301
2019 Novel TG-FGFR1 and TRIM33-NTRK1 transcript fusions in papillary thyroid carcinoma. Genes, chromosomes & cancer 27 30664823
2022 TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex. Cell reports 26 36261009
2017 TRIM33 is essential for osteoblast proliferation and differentiation via BMP pathway. Journal of cellular physiology 26 28063228
2022 TRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2-mediated degradation. EMBO reports 25 35785414
2016 The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation. Proceedings of the National Academy of Sciences of the United States of America 25 27247387
2019 TRIM33 deficiency in monocytes and macrophages impairs resolution of colonic inflammation. EBioMedicine 24 31130476
2012 Tif1γ is essential for the terminal differentiation of mammary alveolar epithelial cells and for lactation through SMAD4 inhibition. Development (Cambridge, England) 24 23154409
2015 Trim33 Binds and Silences a Class of Young Endogenous Retroviruses in the Mouse Testis; a Novel Component of the Arms Race between Retrotransposons and the Host Genome. PLoS genetics 23 26624618
2022 E3 ubiquitin ligase Trim33 ubiquitylates Annexin A2 to promote NF-κB induced skin inflammation in psoriasis. Journal of dermatological science 22 36096861
2012 Dynamic regulation of Tgf-B signaling by Tif1γ: a computational approach. PloS one 22 22461896
2018 Desuppression of TGF-β signaling via nuclear c-Abl-mediated phosphorylation of TIF1γ/TRIM33 at Tyr-524, -610, and -1048. Oncogene 21 30177833
2024 TRIM33 promotes glycolysis through regulating P53 K48-linked ubiquitination to promote esophageal squamous cell carcinoma growth. Cell death & disease 20 39389957
2019 Up-regulation of TIF1γ by valproic acid inhibits the epithelial mesenchymal transition in prostate carcinoma through TGF-β/Smad signaling pathway. European journal of pharmacology 20 31323225
2017 Expression of the autoantigen TRIM33/TIF1γ in skin and muscle of patients with dermatomyositis is upregulated, together with markers of cellular stress. Clinical and experimental dermatology 20 28639716
2017 Trim33 is essential for macrophage and neutrophil mobilization to developmental or inflammatory cues. Journal of cell science 20 28724755
2020 Transcriptional intermediary factor 1 (TIF1) and anti-TIF1γ antibody-positive dermatomyositis. Immunological medicine 19 32649853
2022 A Commercial Anti-TIF1γ ELISA Is Superior to Line and Dot Blot and Should Be Considered as Part of Routine Myositis-Specific Antibody Testing. Frontiers in immunology 18 35154119
2023 Deubiquitinase YOD1 suppresses tumor progression by stabilizing E3 ligase TRIM33 in head and neck squamous cell carcinoma. Cell death & disease 16 37573347
2020 Local ALK-Positive Histiocytosis With Unusual Morphology and Novel TRIM33-ALK Gene Fusion. International journal of surgical pathology 16 33243034
2016 Trim33/Tif1γ is involved in late stages of granulomonopoiesis in mice. Experimental hematology 16 27130375
2014 Imbalanced expression of Tif1γ inhibits pancreatic ductal epithelial cell growth. American journal of cancer research 16 24959375
2021 TRIM33 gene somatic mutations identified by next generation sequencing in neoplasms of patients with anti-TIF1γ positive cancer-associated dermatomyositis. Rheumatology (Oxford, England) 15 33764396
2020 TRIM33 Overexpression Inhibits the Progression of Clear Cell Renal Cell Carcinoma In Vivo and In Vitro. BioMed research international 15 32908919
2016 SnoN suppresses TGF-β-induced epithelial-mesenchymal transition and invasion of bladder cancer in a TIF1γ-dependent manner. Oncology reports 15 27430247
2020 Clinical features of anti-transcription intermediary factor 1γ (TIF1γ)-positive dermatomyositis with internal malignancy and investigation of the involvement of TIF1γ expression in tumors in the pathogenesis of cancer-associated dermatomyositis. The Journal of dermatology 14 32734678
2013 Smad4 and Trim33/Tif1γ redundantly regulate neural stem cells in the developing cortex. Cerebral cortex (New York, N.Y. : 1991) 14 23765158
2022 Machine Learning Algorithms Identify Clinical Subtypes and Cancer in Anti-TIF1γ+ Myositis: A Longitudinal Study of 87 Patients. Frontiers in immunology 13 35237262
2021 Anti-transcription intermediary factor 1 gamma (TIF1γ) antibody-positive dermatomyositis associated with ascending colon cancer: a case report and review of the literature. Journal of medical case reports 13 33745453
2020 PIAS1 and TIF1γ collaborate to promote SnoN SUMOylation and suppression of epithelial-mesenchymal transition. Cell death and differentiation 13 32770107
2022 TRIM33 Modulates Inflammation and Airway Remodeling of PDGF-BB-Induced Airway Smooth-Muscle Cells by the Wnt/β-Catenin Pathway. International archives of allergy and immunology 12 35636393
2022 KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis. Immunity, inflammation and disease 12 36301038
2021 Clinical and laboratory parameters predicting cancer in dermatomyositis patients with anti-TIF1γ antibodies. Journal of dermatological science 12 34772582
2019 Interplay between FACT subunit SPT16 and TRIM33 can remodel chromatin at macrophage distal regulatory elements. Epigenetics & chromatin 12 31331374
2011 Adenovirus E4-ORF3-dependent relocalization of TIF1α and TIF1γ relies on access to the Coiled-Coil motif. Virology 12 22123502
2022 The lncRNA TCONS_00021785/miR-21-5p/Trim33 axis regulates VMP1-mediated zymophagy, reduces the activation of trypsinogen, and promotes acinar cell recovery. Cell death discovery 11 35169128
2022 The crystallin alpha B (HSPB5)-tripartite motif containing 33 (TRIM33) axis mediates myocardial fibrosis induced by angiotensinogen II through transforming growth factor-β (TGF-β1)-Smad3/4 signaling. Bioengineered 11 35333698
2022 Recruitment of TRIM33 to cell-context specific PML nuclear bodies regulates nodal signaling in mESCs. The EMBO journal 11 36524443
2017 Role of TRIM33 in Wnt signaling during mesendoderm differentiation. Science China. Life sciences 11 28844090
2018 Anti-TIF1γ antibody and the expression of TIF1γ in idiopathic inflammatory myopathies. International journal of rheumatic diseases 10 30398003
2024 Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation. Science immunology 9 38608038
2024 TRIM33 enhances the ubiquitination of TFRC to enhance the susceptibility of liver cancer cells to ferroptosis. Cellular signalling 9 38909931
2022 Downregulation of TRIM33 Promotes Survival and Epithelial-Mesenchymal Transition in Gastric Cancer. Technology in cancer research & treatment 9 35929141
2014 New gene evolution in the bonus-TIF1-γ/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network. Molecular biology and evolution 9 24881051
2025 DMC-BH derivative DMC-GF inhibits the growth of glioma stem cells by targeting the TRIM33/SLC25A1/mitochondrial oxidative phosphorylation pathway. Journal of translational medicine 7 40128751
2023 Trim33 masks a non-transcriptional function of E2f4 in replication fork progression. Nature communications 7 37612308
2017 Trim33 regulates early maturation of mouse embryoid bodies in vitro. Biochemistry and biophysics reports 7 29090280
2013 [Association of mutation and methylation in the promoter region of TIF1γ with non-small cell lung cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 7 23676978
2022 Exploiting ELIOT for Scaffold-Repurposing Opportunities: TRIM33 a Possible Novel E3 Ligase to Expand the Toolbox for PROTAC Design. International journal of molecular sciences 5 36430693
2024 TIF1γ and SMAD4 regulation in colorectal cancer: impact on cell proliferation and liver metastasis. Biological chemistry 4 38270141
2024 TRIM33 plays a critical role in regulating dendritic cell differentiation and homeostasis by modulating Irf8 and Bcl2l11 transcription. Cellular & molecular immunology 4 38822080
2021 Alteration of TRIM33 Expression at Transcriptional and Translational Levels is Correlated with Autism Symptoms. Journal of molecular neuroscience : MN 4 33481220
2019 Trim33 is required for appropriate development of pre-cardiogenic mesoderm. Developmental biology 4 30940539
2019 Trim33 (Tif1γ) is not required for skeletal muscle development or regeneration but suppresses cholecystokinin expression. Scientific reports 4 31811178
2025 Anti-Mi2 autoantibodies target PHD fingers of SP140L and TIF1γ, while anti-TIF1γ autoantibodies primarily bind TIF1γ outside the PHD region. Rheumatology (Oxford, England) 3 40795062
2025 SAT1 promotes the progression of OA by regulating TRIM33-mediated p53 acetylation to enhance ferroptosis. PloS one 3 41060973
2024 TRIM33 loss in multiple myeloma is associated with genomic instability and sensitivity to PARP inhibitors. Scientific reports 3 38627415
2023 Age distribution and prevalence in different age groups of four myositis-specific autoantibodies, including anti-ARS, anti-MDA5, anti-Mi-2, and anti-TIF1γ antibodies. The Journal of dermatology 3 36890683
2025 TRIM33 loss reduces androgen receptor transcriptional output and H2BK120 ubiquitination. Communications biology 2 40646276
2022 Trim33 conditions the lifespan of primitive macrophages and onset of definitive macrophage production. Development (Cambridge, England) 2 36052696
2026 Parthenolide ameliorates inflammation in sepsis via covalently targeting Trim33 and inhibiting NF-κB pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 1 41702258
2025 Low TIF1γ Expression is Associated with Cancer Aggressiveness and Shorter Recurrence-Free Survival in Patients with Esophageal Squamous Cell Carcinoma. Annals of surgical oncology 1 40208493
2024 Sequence Alignment between TRIM33 Gene and Human Noncoding RNAs: A Potential Explanation for Paraneoplastic Dermatomyositis. Journal of personalized medicine 1 38929849

Missed literature

Know a paper Affinage missed for TRIM33? Flag it for the maintainers and the community.

No submissions yet.