TRIM24 (tripartite motif-containing 24)

2006-12-01   Jean-Loup Huret 

Identity

HGNC
LOCATION
7q33
LOCUSID
ALIAS
PTC6,RNF82,TF1A,TIF1,TIF1A,TIF1ALPHA,hTIF1
FUSION GENES

DNA/RNA

Description

The TRIM24 gene is organized in 19 exons. There are 2 corresponding transcripts, which give rise to 2 different isoforms (alternative splicing), the first one being shorter.
transcript = 3905 bp; protein = 1016 amino acids; transcript = 4007 bp; protein = 1050 amino acids.

Proteins

Atlas Image

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

Implicated in

Entity name
t(7;8)(q34;p11) in leukemia --> TRIM24 - FGFR1
Cytogenetics
t(7;8)(q34;p11)
Hybrid gene
TRIM24-FGFR1; FGFR1-TRIM24
Fusion 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.
Entity name
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).
Fusion 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?

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
1560934220058p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.Belloni E et al
153221352004TIF1delta, a novel HP1-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids.Khetchoumian K et al
104390471999The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas.Klugbauer S et al
89786961996A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors.Le Douarin B et al
91152741997Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1.Thénot S et al
168802682006Role of TIF1alpha as a modulator of embryonic transcription in the mouse zygote.Torres-Padilla ME et al

Other Information

Locus ID:

NCBI: 8805
MIM: 603406
HGNC: 11812
Ensembl: ENSG00000122779

Variants:

dbSNP: 8805
ClinVar: 8805
TCGA: ENSG00000122779
COSMIC: TRIM24

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000122779ENST00000343526O15164
ENSG00000122779ENST00000415680O15164
ENSG00000122779ENST00000415680A0A024R784

Expression (GTEx)

0
5
10
15
20
25

Pathways

PathwaySourceExternal ID
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by FGFR in diseaseREACTOMER-HSA-1226099
Signaling by FGFR1 in diseaseREACTOMER-HSA-5655302
FGFR1 mutant receptor activationREACTOMER-HSA-1839124
Signaling by cytosolic FGFR1 fusion mutantsREACTOMER-HSA-1839117
Oncogenic MAPK signalingREACTOMER-HSA-6802957
Signaling by BRAF and RAF fusionsREACTOMER-HSA-6802952

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
211644802010TRIM24 links a non-canonical histone signature to breast cancer.153
272380812016TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.59
120969142002Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing nuclear cofactors: a potential mechanism for regulating the switch between coactivation and corepression.36
244690532015TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway.31
199097752009TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells.29
214354352011Prognostic significance of TRIM24/TIF-1α gene expression in breast cancer.24
226663762012Overexpression of TRIM24 correlates with tumor progression in non-small cell lung cancer.24
248204182014TRIM24 is a p53-induced E3-ubiquitin ligase that undergoes ATM-mediated phosphorylation and autodegradation during DNA damage.24
291299082017TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma.22
237175052013TRIM24 overexpression is common in locally advanced head and neck squamous cell carcinoma and correlates with aggressive malignant phenotypes.21

Citation

Jean-Loup Huret

TRIM24 (tripartite motif-containing 24)

Atlas Genet Cytogenet Oncol Haematol. 2006-12-01

Online version: http://atlasgeneticsoncology.org/gene/504/trim24

Historical Card

2006-02-01 TRIM24 (tripartite motif-containing 24) by  Elena Belloni,Pier Giuseppe Pelicci,Pier Paolo Di Fiore 

IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, and IEO, Istituto Europero di Oncologia, Milan, Italy