| 2006 |
TIF1γ (TRIM33) selectively binds receptor-phosphorylated Smad2/3 in competition with Smad4, forming a distinct effector arm of the TGFβ pathway. In human hematopoietic cells, TIF1γ mediates erythroid differentiation response while Smad4 mediates the antiproliferative response downstream of TGFβ. |
Co-immunoprecipitation, GST pulldown, siRNA knockdown in human hematopoietic stem/progenitor cells with functional differentiation and proliferation readouts |
Cell |
High |
16751102
|
| 1999 |
TIF1γ contains RING finger, B-box, coiled-coil, PHD/TTC, and bromodomain architecture. Unlike TIF1α, it does not interact with nuclear receptors or HP1 proteins; unlike TIF1β, it does not interact with the KRAB silencing domain. Deletion of the TIF1 signature sequence (TSS) abrogates its transcriptional repression activity. |
Yeast two-hybrid, GST pulldown, domain-deletion transfection reporter assays in mammalian cells |
Oncogene |
High |
10022127
|
| 2010 |
TIF1γ controls erythroid cell fate by promoting transcription elongation: it physically interacts with the blood-specific SCL transcription complex and positive elongation factors p-TEFb and FACT, and recruits them to erythroid genes to counteract RNA Pol II pausing. Loss-of-function of Pol II-associated factors PAF or DSIF rescued erythroid transcription in tif1γ-deficient zebrafish. |
Genetic epistasis in zebrafish moonshine mutants, co-immunoprecipitation of TIF1γ with SCL complex/p-TEFb/FACT, ChIP in human CD34+ cells |
Cell |
High |
20603019
|
| 2011 |
The PHD finger-bromodomain of TIF1γ/TRIM33 constitutes a multivalent histone-binding module that specifically recognizes histone H3 tails unmethylated at K4 and R2 and acetylated at key lysines. This chromatin binding activates TIF1γ's E3 ubiquitin ligase activity toward Smad4 and its transcriptional repressor activity. |
Histone peptide binding assays, in vitro ubiquitination assays, PHD-bromodomain mutagenesis, chromatin immunoprecipitation |
Molecular Cell |
High |
21726812
|
| 2011 |
TRIM24, TRIM28, and TRIM33 physically associate to form at least two macromolecular complexes (TRIM24-TRIM33 and TRIM24-TRIM28-TRIM33), and somatic hepatocyte-specific inactivation of any of these three proteins promotes hepatocellular carcinoma in mice in a cell-autonomous manner. |
Protein purification and mass spectrometry, conditional knockout mouse models with HCC phenotype assessment |
PNAS |
High |
21531907
|
| 2011 |
TIF1γ forms complexes with TAL1 or PU.1 in hematopoietic cells, occupies specific subsets of their DNA binding sites in vivo, and represses their transcriptional activity, regulating adult hematopoietic stem cell function. |
Co-immunoprecipitation, ChIP, conditional knockout mouse models with HSC transplantation and differentiation assays |
Cell Stem Cell |
High |
21474105
|
| 2015 |
TRIM33, acting as an E3 ubiquitin ligase, targets nuclear β-catenin for degradation in a GSK-3β- and β-TrCP-independent manner. Protein kinase Cδ phosphorylates β-catenin at Ser715, which is required for the TRIM33-β-catenin interaction and subsequent ubiquitination. |
Co-immunoprecipitation, in vitro ubiquitination assays, PKCδ kinase assays, knockdown/overexpression with tumor growth readouts |
Nature Communications |
High |
25639486
|
| 2013 |
TRIM33 is recruited to DNA damage sites in a PARP1- and ALC1-dependent manner, and interacts with ALC1 after DNA damage. TRIM33-deficient cells show enhanced sensitivity to DNA damage and prolonged ALC1 retention at damage sites; overexpression of TRIM33 alleviates DNA repair defects caused by ALC1 overexpression. |
Proteomic analysis (AP-MS), live-cell imaging of TRIM33 recruitment to laser damage sites, siRNA knockdown with DNA damage sensitivity assays |
Journal of Biological Chemistry |
High |
23926104
|
| 2015 |
TRIM33 prevents apoptosis in B lymphoblastic leukemia by associating with a single PU.1-bound enhancer upstream of the pro-apoptotic gene Bim; TRIM33 is recruited by PU.1 to this enhancer and antagonizes PU.1 function. Deletion of this enhancer renders TRIM33 dispensable for leukemia cell survival. |
ChIP-seq, enhancer deletion by genome editing, shRNA knockdown with apoptosis readout |
eLife |
High |
25919951
|
| 2015 |
TRIM33 switches off Ifnb1 transcription during late-phase macrophage activation by being recruited by PU.1 to a conserved Ifnb1 Control Element (ICE) 15 kb upstream of Ifnb1. At ICE, TRIM33 regulates enhanceosome loading, controls chromatin structure, and represses Ifnb1 transcription by preventing recruitment of CBP/p300. |
ChIP, ChIP-seq, 3C/4C chromatin interaction assays, TRIM33 KO macrophages with LPS stimulation, ChIP for CBP/p300 |
Nature Communications |
High |
26592194
|
| 2019 |
TRIM33 (E3 RING ligase) promotes degradation of HIV-1 integrase via the ubiquitin-proteasome system. TRIM33 knockdown in CD4+ cells increases HIV-1 replication and proviral DNA formation; overexpression has opposite effects. |
RNAi screen against ubiquitin machinery components, high-content microscopy, TRIM33 KD and OE with HIV infection assays, proviral DNA quantification |
Nature Communications |
High |
30804369
|
| 2014 |
TIF1γ operates as a SUMO E3 ligase (not only a ubiquitin E3 ligase) that promotes sumoylation of SnoN1 at distinct lysine residues via a 16-amino acid peptide unique to SnoN1 (not SnoN2). TIF1γ-induced SnoN1 sumoylation is required to suppress TGFβ-induced EMT in 3D mammary epithelial organoids. |
Interaction proteomics, in vitro sumoylation assays, domain mapping, 3D NMuMG organoid EMT assay |
Journal of Biological Chemistry |
High |
25059663
|
| 2013 |
TIF1γ sumoylation is required for its repressive activity on TGFβ signaling. TIF1γ interacts with Ubc9 (the SUMO-conjugating enzyme) and is sumoylated at four functional sites within its middle domain (the Smad interaction domain). A sumoylation-defective mutant significantly reduces TIF1γ inhibition of Smad complexes and Smad4 binding to the PAI-1 promoter. |
Co-immunoprecipitation, site-directed mutagenesis of sumoylation sites, ChIP on PAI-1 promoter, EMT assay in mammary epithelial cells |
Journal of Cell Science |
High |
23788427
|
| 2018 |
Nuclear c-Abl tyrosine kinase phosphorylates TIF1γ/TRIM33 at Tyr-524, Tyr-610, and Tyr-1048, which reduces TIF1γ association with Smad3 and de-suppresses TGFβ signaling. EGF activates c-Abl to increase TIF1γ tyrosine phosphorylation, synergizing with TGFβ to provoke EMT. |
Phosphorylation site identification, triple tyrosine-to-phenylalanine (3YF) mutant rescue experiments, co-immunoprecipitation of TIF1γ with Smad3, EGF stimulation assays |
Oncogene |
High |
30177833
|
| 2018 |
TRIM33 is required for Th17 cell proinflammatory function: it associates with Smad2 and is recruited to the Il17a and Il10 gene loci in a Smad2-dependent manner, mediating chromatin remodeling during Th17 differentiation to induce IL-17 and suppress IL-10 expression. |
Conditional T cell-specific TRIM33 KO mice, ChIP at Il17a and Il10 loci, in vitro Th17 differentiation assays, autoimmune disease model |
Journal of Experimental Medicine |
High |
29930104
|
| 2016 |
Adenovirus E4-ORF3 protein acts as a SUMO E3 ligase for TIF1γ sumoylation and can extend poly-SUMO3 chains in vitro; E4-ORF3 self-assembly (multimerization) is required for these activities. E4-ORF3 binds TIF1γ through the Coiled-Coil domain and relocalizes it to nuclear track structures in infected cells. |
In vitro sumoylation reconstitution with purified E4-ORF3 and TIF1γ, SUMO chain elongation assays, E4-ORF3 multimerization mutants, co-immunoprecipitation |
PNAS |
High |
27247387
|
| 2020 |
TRIM33 directly associates with HSPB5 (crystallin alpha B), which diminishes TRIM33 protein level and impairs TRIM33/SMAD4 interaction. TRIM33 acts as a negative regulator of TGFβ1/SMAD signaling in lung fibroblasts and macrophages; its loss increases TGFβ1 secretion and downstream fibrogenic gene expression. |
Direct binding assay (HSPB5-TRIM33), co-immunoprecipitation, conditional KO mouse with bleomycin-induced fibrosis, primary cell cultures |
European Respiratory Journal |
High |
32184320
|
| 2014 |
Tif1γ controls TGFβ1 receptor (Tgfbr1) turnover: Tif1γ-deficient HSCs have elevated Tgfbr1 levels and increased TGFβ sensitivity. Two HSC populations discriminated by Tgfbr1 expression level (myeloid-biased Tgfbr1-high vs. balanced Tgfbr1-low) are regulated by Tif1γ. |
Conditional HSC-specific Tif1γ KO mice, flow cytometry, aging phenotype analysis, Tgfbr1 expression and TGFβ signaling assays |
PNAS |
Medium |
25002492
|
| 2022 |
TRIM33 facilitates androgen receptor (AR) chromatin binding and directly regulates AR-driven transcription in prostate cancer. TRIM33 also protects AR from Skp2-mediated ubiquitination and proteasomal degradation. |
Proteomics to identify TRIM33 as AR interactor, Co-IP, ChIP-seq for AR with TRIM33 KD, ubiquitination assays with Skp2 |
EMBO Reports |
High |
35785414
|
| 2015 |
TIF1γ inhibits TGFβ-induced EMT in mammary epithelial cells by competing with Smad4 for binding to Smad2/3, and directly binds and represses the PAI-1 (plasminogen activator inhibitor 1) promoter. |
siRNA knockdown of TIF1γ or Smad4, microarray analysis of TIF1γ target genes, ChIP on PAI-1 promoter, EMT assays |
EMBO Reports |
High |
21597466
|
| 2021 |
TIF1γ directly controls coenzyme Q (CoQ) synthesis gene expression through transcription elongation, and CoQ levels regulate mitochondrial respiration. Loss of tif1γ reduces CoQ levels and increases the succinate/α-ketoglutarate ratio, leading to increased histone methylation and impaired erythroid differentiation. |
Chemical suppressor screen in zebrafish tif1γ mutants, metabolomics (CoQ measurement), histone methylation assays, CoQ analog rescue of bloodless phenotype |
Science |
High |
33986176
|
| 2024 |
The TRIM33 bromodomain is the sole bromodomain (among 28 tested) that binds histone lysine lactylation (Kla) peptides. A unique glutamic acid residue within the TRIM33 bromodomain binding pocket confers specificity for Kla over other modifications; mutagenesis of this glutamic acid eliminates Kla binding. |
AlphaScreen assay of 28 bromodomains, isothermal titration calorimetry, protein-detected NMR, site-directed mutagenesis, molecular modeling |
ACS Chemical Biology |
High |
39556662
|
| 2019 |
In macrophages, TRIM33 interacts with FACT subunit SPT16 at PU.1-bound distal regulatory elements. TRIM33 deficiency leads to FACT release, loss of positioned nucleosomes, RNA Pol II recruitment and bidirectional transcription at these elements, and increased gene expression. |
ChIP-seq for SPT16 and TRIM33, co-immunoprecipitation of TRIM33 with SPT16, ChIP for RNA Pol II and histone marks in TRIM33 KO macrophages, 3C chromatin interaction |
Epigenetics & Chromatin |
High |
31331374
|
| 2017 |
In zebrafish, Trim33 deficiency causes primitive macrophages to fail to colonize the CNS to become microglia; both macrophages and neutrophils display reduced basal interstitial motility and fail to respond to inflammatory recruitment signals. Mouse Trim33-deficient bone marrow-derived macrophages show strongly reduced 3D amoeboid mobility in collagen gels. |
Trim33-deficient zebrafish embryo live imaging, bacterial infection assays, 3D collagen gel motility assay for mouse BMDMs |
Journal of Cell Science |
High |
28724755
|
| 2015 |
TIF1γ inactivation causes chromosomal defects due to attenuation of the spindle assembly checkpoint and the post-mitotic checkpoint, resulting in loss of contact growth inhibition and increased anchorage-independent growth. |
TIF1γ siRNA knockdown, mitotic checkpoint assays, chromosomal instability quantification, soft agar and in vivo tumor growth assays |
Cancer Research |
Medium |
26282171
|
| 2023 |
TRIM33 ubiquitin ligase targets E2f4 for degradation in unperturbed cells, limiting E2f4 genomic binding and interactions with DNA helicase Recql. Replicative stress blunts TRIM33-dependent ubiquitination of E2f4, stimulating transient Recql recruitment to chromatin and facilitating recovery of DNA synthesis. |
TRIM33 deletion in mouse cells, ubiquitination assays for E2f4, ChIP-seq for E2f4 and Recql, DNA fiber assays for replication fork progression, Myc-overexpression tumor model |
Nature Communications |
High |
37612308
|
| 2022 |
TRIM33 promotes K63-linked ubiquitination of Annexin A2 (Anxa2) in keratinocytes, which promotes Anxa2 interaction with p50/p65 NF-κB subunits, favors nuclear retention of p50/p65, and drives expression of NF-κB downstream inflammatory genes. |
Immunoprecipitation-mass spectrometry to identify Anxa2 as TRIM33 substrate, K63-ubiquitination assay, co-immunoprecipitation of Anxa2 with NF-κB subunits, nuclear fractionation |
Journal of Dermatological Science |
Medium |
36096861
|
| 2020 |
TRIM33 protects osteoblasts from oxidative stress-induced apoptosis by binding CBP and restraining CBP-mediated FOXO3a acetylation, thereby attenuating FOXO3a ubiquitylation and degradation. TRIM33 and FOXO3a co-localize in osteoblast nuclei. |
Co-immunoprecipitation of TRIM33 with CBP and FOXO3a, immunofluorescence co-localization, FOXO3a acetylation and ubiquitination assays, OVX mouse model |
Aging Cell |
Medium |
34101965
|
| 2024 |
TRIM33 promotes K48-linked polyubiquitination and proteasomal degradation of p53 at the K351 site in esophageal squamous cell carcinoma, leading to upregulation of glycolysis target genes GLUT1, HK2, PKM2, and LDHA. |
Co-immunoprecipitation, in vitro/cell-based ubiquitination assays with K48-linkage specificity, K351 site mutagenesis, glycolysis assays, xenograft model |
Cell Death & Disease |
Medium |
39389957
|
| 2022 |
TRIM33 co-localizes with promyelocytic leukemia nuclear bodies (PML-NBs) specifically in mouse ESCs, and this localization depends on PML. TRIM33 and PML co-regulate Lefty1/2 expression, with PML-NBs directly associating with Lefty1/2 gene loci and required for TRIM33 recruitment to these loci. |
Co-localization imaging, TurboID proximity-labeling proteomics, PML KO in mESCs, ChIP, 4C-seq |
EMBO Journal |
High |
36524443
|
| 2017 |
TRIM33 has E3 ubiquitin ligase activity toward A-MYB, regulating its abundance in the testis. ChIP-seq in mouse testis reveals TRIM33 is enriched at RLTR10B LTR elements of MMERVK10C retrotransposons, and Trim33 haploinsufficiency increases expression of genes transcribed from upstream RLTR10B. |
ChIP-seq in mouse testis, RNA-seq, A-MYB ubiquitination assay |
PLoS Genetics |
Medium |
26624618
|
| 2022 |
TRIM33 interacts with TFRC (transferrin receptor) and promotes its E3 ligase-dependent ubiquitination and degradation, thereby inducing cellular ferroptosis in hepatocellular carcinoma cells. |
Co-immunoprecipitation, ubiquitination assay, ferroptosis markers (MDA, Fe2+, mitochondrial superoxide), xenograft model |
Cellular Signalling |
Medium |
38909931
|
| 2020 |
PIAS1 and TIF1γ collaborate as SUMO E3 ligases forming a trimeric complex with SnoN to promote SnoN SUMOylation in an interdependent manner, suppressing EMT in breast organoids. |
Co-immunoprecipitation of trimeric SnoN-TIF1γ-PIAS1 complex, in vitro SUMOylation assays, loss-of-function studies in 3D breast organoid EMT assay |
Cell Death and Differentiation |
High |
32770107
|
| 2022 |
TIF1γ binds to TBP in competition with TAF15 and impedes TAF15/TBP-mediated IL-6 transactivation. TIF1γ also modifies TAF15 through multi-mono-ubiquitylation and drives nuclear export of TAF15, thereby inhibiting EMT and metastasis of lung adenocarcinoma cells. |
Co-immunoprecipitation of TIF1γ-TBP and TIF1γ-TAF15 interactions, ubiquitination assay for TAF15, nuclear/cytoplasmic fractionation, IL-6 luciferase reporter, EMT and metastasis assays |
Cell Reports |
Medium |
36261009
|
| 2024 |
TRIM33 is an essential regulator of the entire DC lineage: conditional deletion causes rapid loss of DC progenitors, pDCs, and cDC1s. Trim33-deficient Flt3+ progenitors up-regulate pro-inflammatory and macrophage-specific genes but fail to induce the DC differentiation program, placing TRIM33 upstream of IRF8-driven DC commitment. |
Genome-wide CRISPR-Cas9 screen for Flt3L-driven DC differentiation, conditional Trim33 KO mice, RNA-seq of progenitors |
Science Immunology |
High |
38608038
|
| 2024 |
TRIM33 promotes transcription of Irf8 in DC progenitors by maintaining CDK9 and Ser2-phosphorylated RNA Pol II levels at Irf8 gene sites (consistent with a transcription elongation function). TRIM33 also directly suppresses PU.1-mediated transcription of Bcl2l11 (Bim) to prevent DC apoptosis. |
ChIP for CDK9 and S2-phospho-Pol II at Irf8 locus, ChIP for TRIM33 and PU.1 at Bcl2l11, conditional KO mice, differentiation and apoptosis assays |
Cellular & Molecular Immunology |
High |
38822080
|
| 2017 |
TRIM33 is essential for the production of small peritoneal macrophages, monocytes, and bone marrow-derived macrophages. In mature myeloid cells, TRIM33 ChIP-seq reveals binding near inflammatory response genes; TRIM33 loss impairs repression of late LPS activation pathways and causes high LPS sensitivity in vivo. |
ChIP-seq in immature and mature myeloid cell lines, conditional KO mice with in vivo LPS challenge, macrophage production assays |
Oncotarget |
Medium |
27974684
|
| 2023 |
TRIM21 E3 ubiquitin ligase forms a complex with TIF1γ in the nucleus and promotes K48-linked ubiquitination of TIF1γ at K5, leading to TIF1γ degradation and consequent increase in nuclear β-catenin presence in glioblastoma. |
TMT/MS to identify TRIM21 substrates including TIF1γ, Co-IP, K48-ubiquitination assay at K5, luciferase reporter for β-catenin, RING-finger deletion mutant, xenograft model |
Theranostics |
Medium |
37771771
|
| 2023 |
YOD1 deubiquitinase stabilizes TRIM33 by suppressing its ubiquitination and degradation, thereby inhibiting ERK/β-catenin pathway activation in head and neck squamous cell carcinoma. |
Co-immunoprecipitation of YOD1 with TRIM33, ubiquitination assay showing YOD1 reduces TRIM33 ubiquitination, KD/OE functional assays with ERK/β-catenin pathway readout |
Cell Death & Disease |
Medium |
37573347
|
| 2025 |
TRIM33 loss reduces H2BK120 ubiquitination levels and decreases AR transcriptional output without affecting AR protein stability, suggesting TRIM33 facilitates maximal AR activity through chromatin modification rather than AR stabilization. |
Co-immunoprecipitation and ChIP-seq across prostate cancer cell lines, H2BK120 ubiquitination measurement, AR stability assays with TRIM33 KD |
Communications Biology |
Medium |
40646276
|
| 2017 |
TRIM33 positively regulates osteoblast differentiation through the BMP pathway by forming a TRIM33-Smad1/5 complex; this interaction triggers phosphorylation of Smad1/5 and promotes BMP-driven differentiation. |
Co-immunoprecipitation of TRIM33 with Smad1/5, phospho-Smad1/5 assay, TRIM33 overexpression/knockdown with ALP, Runx2, osteocalcin readouts, cell cycle assays |
Journal of Cellular Physiology |
Medium |
28063228
|