The TFG‐TEC oncoprotein induces transcriptional activation of the human β‐enolase gene via chromatin modification of the promoter region

  title={The TFG‐TEC oncoprotein induces transcriptional activation of the human $\beta$‐enolase gene via chromatin modification of the promoter region},
  author={Ah-young Kim and Bobae Lim and JeeHyun Choi and Jungho Kim},
  journal={Molecular Carcinogenesis},
Recurrent chromosome translocations are the hallmark of many human cancers. A proportion of human extraskeletal myxoid chondrosarcomas (EMCs) are associated with the characteristic chromosomal translocation t(3;9)(q11–12;q22), which results in the formation of a chimeric protein in which the N‐terminal domain of the TRK‐fused gene (TFG) is fused to the translocated in extraskeletal chondrosarcoma (TEC; also called CHN, CSMF, MINOR, NOR1, and NR4A3) gene. The oncogenic effect of this… 
The Trk fused gene-product (Tfg) is part of a 600-700kDa CARMA1 complex
Nik-binding protein (NIBP), Ras-GAP SH3 binding protein 2 (G3BP1) and Trk-fused gene (Tfg) were identified by peptide mass fingerprinting in immunopurified CARMA1 complexes and the interaction of Tfg andCARMA1 was confirmed by co-immunoprecipitation and Blue native polyacrylamide gel electrophoresis.
Enhancer hijacking activates oncogenic transcription factor NR4A3 in acinic cell carcinomas of the salivary glands
It is concluded that NR4A3 is upregulated through enhancer hijacking and has important oncogenic functions in AciCC.
Metabolomic and lipidomic signatures associated with activation of human cDC1 (BDCA3+/CD141+) dendritic cells
This work mapped metabolomic and lipidomic signatures associated with the activation phenotype of human conventional DC type 1, a DC subset specialized in cross‐presentation and therefore of major importance for the stimulation of CD8+ T cells, and highlighted the metabolic adaptations required for cDC1 maturation.
Accurate and highly interpretable prediction of gene expression from histone modifications
ShallowChrome is proposed, a novel computational pipeline to model transcriptional regulation via HMs in both an accurate and interpretable way, and state-of-the-art results on the binary classification of gene transcriptional states over 56 cell-types from the REMC database, largely outperforming recent deep learning approaches.
Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host
Analysis of transcriptional activity of the periodontal pocket microbiota from all domains of life as well as the human host in health and chronic periodontitis provides evidence for the potentially severe impact of the dysbiotic microbiota on human health.
Metalloproteomic Strategies for Identifying Proteins as Biomarkers of Mercury Exposure in Serrasalmus rhombeus from the Amazon Region
Nine proteins with characteristics of biomarkers of mercury exposure are identified, and glutathione peroxidase stands out as an enzyme of great importance in the antioxidant defence of organisms subjected to oxidative stress caused by xenobiotics.
Identification and Validation of Esophageal Squamous Cell Carcinoma Targets for Fluorescence Molecular Endoscopy
GLUT1 was identified and validated as a promising molecular imaging target and it was demonstrated that fluorescent imaging after topical application of 2-DG 800CW can differentiate HGD and ESCC from LGD and normal esophagus.
Extraskeletal Myxoid Chondrosarcoma: A Comparative Study of Imaging and Pathology
13 cases of EMC confirmed by surgery biopsy were retrospectively studied and on MRI, EMC showed lobulated hypersignal intensity on T2WI with characteristic arc, septa, or interval septa enhancement.


The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC.
The results suggest that the oncogenic effect of the t(3;9) translocation may be due to the TFG-TEC chimeric protein and that fusion of theTFG (NTD) to the TEC protein produces a gain-of-function chimeric product.
A TFG-TEC nuclear localization mutant forms complexes with the wild-type TFG-TEC oncoprotein and suppresses its activity.
The results show that the biological functions of the TFG-TEC oncogene can be modulated by a dominant-negative mutant.
The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF‐κB pathway
TFG enhances the effect of TNF‐α, TANK, TNF receptor‐associated factor (TRAF)2, and TRAF6 in inducing NF‐κB activity, and it is suggested that TFG is a novel member of the NF-κB pathway.
The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator
Co-transfection experiments of COS cells and human chondrocytes indicate that whereas TEC moderately activates transcription from a NBRE-containing promoter, the corresponding EWS/TEC fusion protein is a highly potent transcriptional activator of the same promoter, being approximately 270-fold more active than the native receptor.
The hTAFII68‐TEC fusion protein functions as a strong transcriptional activator
Examination of the functional consequences of the fusion of the amino terminal domain of hTAFII68 to TEC in EMC suggests that the oncogenic effect of the t(9;17) translocation may be due to the hTAfII68‐TEC chimeric protein and that fusion of this protein to the TEC protein produces a gain of function chimeric product.
Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.
It is reported that the EWS gene located at chromosome band 22q12 becomes fused to CHN, a member of the steroid/thyroid receptor gene superfamily located at 9q22-31, in a skeletal myxoid chondrosarcoma.
Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.
This work provides the second example of the oncogenic conversion of a nuclear receptor and the first example involving the orphan subfamily, and analysis of the disturbance induced by the EWS/TEc protein in the nuclear receptor network and their target genes may lead to new approaches for EMC treatment.
Structure and expression of the mouse gene encoding the orphan nuclear receptor TEC.
Northern blots and RT-PCR analyses showed that mRNAs encoding both isoforms are expressed in all mouse tissues examined, which suggests that TEC may perform some basic housekeeping cellular function in addition to its role in cell proliferation.
TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.
TFG can provide an alternative to NPM as a fusion partner responsible for activation of the ALK and the pathogenesis of ALCL, showing that the new cloned cDNA sequences are translated into chimeric proteins with functional activity.
Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma.
It is reported that a third member of the EWS, TLS/FUS gene family, TAF2N, can replace EWS as a fusion partner to TEC in EMC.