Download Gene Section CITED4 (Cbp/p300 interacting transactivator, with Glu/Asp

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CITED4 (Cbp/p300-interacting transactivator, with
Glu/Asp-rich carboxy-terminal domain, 4)
Miguel Torres-Martin, Juan Antonio Rey
Unidad de Investigacion del Hospital Universitario La Paz, Madrid, Spain (MTM, JAR)
Published in Atlas Database: August 2009
Online updated version : http://AtlasGeneticsOncology.org/Genes/CITED4ID44535ch1p34.html
DOI: 10.4267/2042/44794
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Description
Identity
CITED4 has a characteristic CITED domain motif
conserved in all CITED peptides located at the
carboxyl-terminal domain that binds with p300/CBP.
Other names: MRG2; MRG-2
HGNC (Hugo): CITED4
Location: 1p34.2
Expression
DNA/RNA
In all tissues with special intensity in heart, liver,
pancreas and skeletal muscle.
Description
Localisation
DNA sequence is located at chromosome 1p.
CITED4 has nuclear and cytoplasmatic location. In
most cells it has a nuclear localization, but in others it
was localized in nucleus and cytoplasm.
Transcription
Transcription consists of a single exon without
alternative splicing. mRNA: NM_133467.
Function
Binds CBP and tumor suppressor protein EP300 by
carboxy terminus domain (residues 138-184).
Therefore it may be implicated in gene transcription.
As other genes of the family, CITED4 physically
interacts with transcription factor AP-2.
Protein
Note
CITED4 protein is 184 amino acid long with a
molecular weight of 18569 Da.
NP_597724.
A. Position of CITED4 in the chromosome 1. B. Flanking genes of CITED4.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(7)
633
CITED4 (Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 4)
Torres-Martin M, Rey JA
Coding and flanking regions of CITED4.
Fox et al. (2002) showed that CITED4 blocks the
binding of hypoxia-inducible factor 1alpha to p300 in
their experiments made in vitro and inhibits hypoxiainducible factor-1alpha transactivation and hypoxiamediated reporter gene activation. That is the reason
why they concluded that CITED4 might be an inhibitor
of hypoxia-inducible factor 1alpha.
Fox et al. (2002). This loss may allow p300/CBP to
interact with hypoxia-inducible factor 1a and
oncogenes to enhance their transcriptional activity
leading to an aggressive tumor phenotype (Fox et al.,
2004).
Prognosis
CITED4 is located in the nucleus in normal tissue, but
in breast tumors is present both nuclear and
cytoplasmatic location. This characteristic might be
used as prognosis factor of this kind of tumors.
Homology
CITED4 has 2 paralogues (CITED1 and CITED2) in
humans. All of them belong to CITED family, found
only in jawed vertebrates to date (Braganca et al.,
2002).
References
Bragança J, Swingler T, Marques FI, Jones T, Eloranta JJ,
Hurst HC, Shioda T, Bhattacharya S. Human CREB-binding
protein/p300-interacting transactivator with ED-rich tail (CITED)
4, a new member of the CITED family, functions as a coactivator for transcription factor AP-2. J Biol Chem. 2002 Mar
8;277(10):8559-65
Mutations
Note
No mutations has been reported yet, but a total of 16
polymorphisms with unknown consequences has been
founded by Tews et al. (2007) and Torres-Martin et al.
(2008).
Yahata T, Takedatsu H, Dunwoodie SL, Bragança J, Swingler
T, Withington SL, Hur J, Coser KR, Isselbacher KJ,
Bhattacharya S, Shioda T. Cloning of mouse Cited4, a member
of the CITED family p300/CBP-binding transcriptional
coactivators: induced expression in mammary epithelial cells.
Genomics. 2002 Dec;80(6):601-13
Implicated in
Oligodendroglioma
Fox SB, Bragança J, Turley H, Campo L, Han C, Gatter KC,
Bhattacharya S, Harris AL. CITED4 inhibits hypoxia-activated
transcription in cancer cells, and its cytoplasmic location in
breast cancer is associated with elevated expression of tumor
cell hypoxia-inducible factor 1alpha. Cancer Res. 2004 Sep
1;64(17):6075-81
Note
CITED4
promoter
is
methylated
in
oligodendrogliomas, especially in those with 1p/19q
deletions. This hypermethylation is responsible of
lower levels of CITED4 mRNA expression, suggesting
a way by which CITED4 is almost silenced by both
hypermethylation and chromosomal deletion (Tews et
al., 2007).
Prognosis
CITED4 hypermethylation in oligodendroglioma
patients is similar to prognosis associated to 1p/19q
deletions. Thus, CITED4 hypermethylation might be an
alternative or even a confirmation of 1p/19q testing.
Tews B, Roerig P, Hartmann C, Hahn M, Felsberg J, Blaschke
B, Sabel M, Kunitz A, Toedt G, Neben K, Benner A, von
Deimling A, Reifenberger G, Lichter P. Hypermethylation and
transcriptional downregulation of the CITED4 gene at 1p34.2 in
oligodendroglial tumours with allelic losses on 1p and 19q.
Oncogene. 2007 Jul 26;26(34):5010-6
Torres-Martín M, Franco-Hernandez C, Martinez-Glez V, de
Campos JM, Isla A, Casartelli C, Rey JA. Mutational analysis
of the CITED4 gene in glioblastomas. Cancer Genet
Cytogenet. 2008 Sep;185(2):114-6
Breast cancer
This article should be referenced as such:
Note
Cytoplasmatic translocation and loss of nuclear
expression has been associated with breast cancer by
Torres-Martin M, Rey JA. CITED4 (Cbp/p300-interacting
transactivator, with Glu/Asp-rich carboxy-terminal domain, 4).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(7):633-634.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(7)
634