Fusion genes
(updated 2016) | NFU1 (2p13.3) / TRIM24 (7q33) | RARA (17q21.2) / TRIM24 (7q33) | RET (10q11.21) / TRIM24 (7q33) |
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ST7 (7q31.2) / TRIM24 (7q33) | TRIM24 (7q33) / BRAF (7q34) | TRIM24 (7q33) / FGFR1 (8p11.23) |
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TRIM24 (7q33) / NTN4 (12q22) | TRIM24 (7q33) / NTRK2 (9q21.33) | TRIM24 (7q33) / RARA (17q21.2) |
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TRIM24 (7q33) / RET (10q11.21) | TRIM24 (7q33) / SVOPL (7q34) | TRIM24 (7q33) / ULK4 (3p22.1) |
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| Description | TRIM24 encodes a nuclear protein, transcription intermediary factor 1a displaying an RBCC motif (RING finger, B-BOX, and coiled-coil domains, also called tripartite motif, TRIM) in its N-terminus and PHD and bromo domains at the C-terminus. The following is a scheme (not drawn to scale) of the protein and its domains. |
| Expression | ubiquitously and early in development, but also in many adult tissues |
| Localisation | The protein localizes to the nucleus (nuclear bodies). |
| Function | Transcriptional regulator of nuclear receptors, including retinoic acid, thyroid, vitamin D3, and estrogen receptors; participates in multiprotein complexes; interacts with numerous proteins involved in chromatin structure; recruitment of TRIM24 to specific sites in the genome would ensure the localization of initiating RNA polII, and of chromatin remodeling complexes; may function through modulation of chromatin states (regulator of higher order chromatin structures, in order to promote silencing on euchromatic genes); TRIM24 has been demonstrated to possess an intrinsic transcriptional silencing activity which requires histone deacetylation; interacts directly with members of the heterochromatin protein 1 family. May be a key regulator of developmental and physiological processes. |
| Homology | TRIM28/TIF1B, TRIM33/TIF1G, TRIM66/TIF1D |
| Note | |
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| Entity | t(7;8)(q34;p11) in leukemia --> TRIM24 - FGFR1 |
| Disease | acute myeloid leukemia (AML), 8p11 myeloproliferative syndrome (EMS). |
| Cytogenetics | t(7;8)(q34;p11) |
| Hybrid/Mutated Gene | TRIM24-FGFR1; FGFR1-TRIM24 |
| Abnormal Protein | The 2 predicted fusion proteins are organized as follows: TRIM24-FGFR1 contains the RING, BBOX and BBC domains from TRIM24 and the TK domain from FGFR1; FGFR1-TRIM24 contains the signal peptide along with the 3 IG-LIKE and transmembrane domains from FGFR1 and the PHD with the BROMO domains from TRIM24. |
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| Entity | t(7;10)(q34;q11) in papillary thyroid carcinoma: --> TRIM24- RET |
| Disease | Found in one case of papillary thyroid carcinoma, in a child (a boy aged 4 yrs) exposed to radioactive fallout after the Chernobyl reactor accident (note: children exposed to Chernobyl radioactive fallout frequently developped papillary thyroid carcinoma (PTC), and a very high prevalence of RET rearrangements was found in these childhood PTC, compared to PTC of adults). |
| Abnormal Protein | Fusion of the 5' end of TRIM24 including the RBCC (RING finger, B-BOX, and coiled-coil domains) motif to the 3' end of RET including the tyrosine kinase domain (and loosing the ligand binding and transmembrane domains of RET). |
| Oncogenesis | The fusion protein could form dimers (via the coiled coil domain) and show constitutive tyrosine phosphorylation? |
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| 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes. |
| Belloni E, Trubia M, Gasparini P, Micucci C, Tapinassi C, Confalonieri S, Nuciforo P, Martino B, Lo-Coco F, Pelicci PG, Di Fiore PP |
| Genes, chromosomes & cancer. 2005 ; 42 (3) : 320-325. |
| PMID 15609342 |
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| TIF1delta, a novel HP1-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids. |
| Khetchoumian K, Teletin M, Mark M, Lerouge T, Cerviño M, Oulad-Abdelghani M, Chambon P, Losson R |
| The Journal of biological chemistry. 2004 ; 279 (46) : 48329-48341. |
| PMID 15322135 |
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| The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas. |
| Klugbauer S, Rabes HM |
| Oncogene. 1999 ; 18 (30) : 4388-4393. |
| PMID 10439047 |
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| A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. |
| Le Douarin B, Nielsen AL, Garnier JM, Ichinose H, Jeanmougin F, Losson R, Chambon P |
| The EMBO journal. 1996 ; 15 (23) : 6701-6715. |
| PMID 8978696 |
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| Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1. |
| Thénot S, Henriquet C, Rochefort H, Cavaillè V |
| The Journal of biological chemistry. 1997 ; 272 (18) : 12062-12068. |
| PMID 9115274 |
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| Role of TIF1alpha as a modulator of embryonic transcription in the mouse zygote. |
| Torres-Padilla ME, Zernicka-Goetz M |
| The Journal of cell biology. 2006 ; 174 (3) : 329-338. |
| PMID 16880268 |
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