Download Gene Section TRIM24 (tripartite motif-containing 24) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Mini Review
TRIM24 (tripartite motif-containing 24)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Published in Atlas Database: December 2006
Online updated version: http://AtlasGeneticsOncology.org/Genes/TRIM24ID504ch7q34.html
DOI: 10.4267/2042/38410
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2007 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Expression
Identity
Ubiquitously and early in development, but also in
many adult tissues.
Hugo: TRIM24
Other names: PTC6; TF1A; TIF1; RNF82; TIF1A;
hTIF1; TIF1ALPHA
Location: 7q34
Localisation
The protein localizes to the nucleus (nuclear bodies).
Function
DNA/RNA
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.
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.
Protein
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.
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2)
Homology
TRIM28/TIF1B, TRIM33/TIF1G, TRIM66/TIF1D.
111
TRIM24 (tripartite motif-containing 24)
Huret JL
Implicated in
Breakpoints
8p12 (FGFR1)
t(7;8)(q34;p11) in leukemia → TRIM24FGFR1
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.
7q34 (TRIM24)
10q11 (RET)
TRIM24 and partners. Editor 08/2005.
References
Le Douarin B, Nielsen AL, Garnier JM, Ichinose H,
Jeanmougin F, Losson R, Chambon P. A possible involvement
of TIF1 alpha and TIF1 beta in the epigenetic control of
transcription by nuclear receptors. EMBO J 1996;15:67016715.
t(7;10)(q34;q11) in papillary thyroid
carcinoma → TRIM24-RET
Thénot S, Henriquet C, Rochefort H, Cavaillès V. Differential
interaction of nuclear receptors with the putative human
transcriptional
coactivator
hTIF1.
J
Biol
Chem
1997;272:12062-12068.
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?
Klugbauer S, Rabes HM. The transcription coactivator HTIF1
and a related protein are fused to the RET receptor tyrosine
kinase in childhood papillary thyroid carcinomas. Oncogene
1999;18:4388-4393.
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2)
Khetchoumian K, Teletin M, Mark M, Lerouge T, Cerviño M,
Oulad-Abdelghani M, Chambon P, Losson R. TIF1delta, a
novel HP1-interacting member of the transcriptional
intermediary factor 1 (TIF1) family expressed by elongating
spermatids. J Biol Chem 2004;279:48329-48341.
Elena Belloni, Maurizio Trubia, Patrizia Gasparini, Carla
Micucci, Cinzia Tapinassi, Stefano Gonfalonieri, Paolo
Nuciforo, Bruno Martino, Francesco Lo Coco, Pier Giuseppe
Pelicci, and Pier Paolo Di Fiore. 8p11 Myeloproliferative
Syndrome with a Novel t(7;8) Translocation Leading to Fusion
of the FGFR1 and TIF1 Genes. Genes Chromosomes Cancer
2005;42:320-325.
Torres-Padilla ME, Zernicka-Goetz M. Role of TIF1 as a
modulator of embryonic transcription in the mouse zygote. J
Cell Biol 2006;174:329-338.
This article should be referenced as such:
Huret JL. TRIM24 (tripartite motif-containing 24). Atlas Genet
Cytogenet Oncol Haematol.2007;11(2):111-112.
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