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Transcript
Atlas of Genetics and Cytogenetics
in Oncology and Haematology
OPEN ACCESS JOURNAL AT INIST-CNRS
Gene Section
Review
DENR (density-regulated protein)
Line S Reinert, Ronald B Gartenhaus
University of Maryland Greenebaum Cancer Center, 9-011 BRB, 655 West Baltimore Street, Baltimore, MD
21201, USA (LSR, RBG)
Published in Atlas Database: June 2008
Online updated version : http://AtlasGeneticsOncology.org/Genes/DENRID40295ch12q24.html
DOI: 10.4267/2042/44465
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Localisation
Identity
Predominantly in the cytoplasm of 3T3 cells.
Other names: DRP; DRP1; SMAP-3
HGNC (Hugo): DENR
Location: 12q24.31
Function
Description
Until recently there was little published data regarding
DENR function. Reinert et al. showed that the
oncogene MCT-1 interacts with DENR in vivo and in
vitro. DENR contains a SUI1 domain which is also
found in translation initiation factor eIF1, where the
SUI1 domain is involved in recognition of the
translation initiation codon (Yoon and Donahue, 1992).
Interestingly, DENR together with MCT-1 sediment in
the translation initiation complex fraction in both
human embryonic kidney cell cultures and lymphoid
cell lines. This complex was shown to interact with the
cap complex and to alter the mRNA translational
profile of a subset of cancer-related mRNAs. This
supports a model where MCT-1 exerts it ongogenic
function, at least in part by recruiting the SUI1 domain
containing DENR to the translation initiation complex,
thereby modulating the translational profile (Reinert et
al., 2006).
Size: 198 amino acids; 22092 Da.
Homology
Expression
The SUI1 domain present in DENR is homologous to
the SUI-1 domain found in eIF1. The SUI1 domain
contains a secondary structure fold corresponding to
that found in a number of ribosomal proteins and RNAbinding domains.
DNA/RNA
Description
The gene encompasses 18583 bp DNA and contains 8
exons (e.g. NCBI: NC_000012).
Transcription
2766 bp mRNA.
The 3'-untranslated region (3' UTR) of DENR was
found to have a high number of uracyl (U)- and adenine
(A)-rich sequences (AREs) (Mazan-Mamczarz and
Gartenhaus, 2007).
Protein
DENR is expressed in variety of tissues, with the
highest quantity in skeletal and cardiac muscle. The
protein level of DENR is up regulated in parallel with
increasing cell density (Deyo et al., 1998). Very
recently, it was found that this up regulation is
controlled by the AUF-1 protein which binds to the
3'UTR of DENR mRNA and in a cell densitydependent manner (Mazan-Mamczarz and Gartenhaus,
2007). Furthermore, Oh JJ. et al. showed that DENR
expression is increased in association with HER-2
overexpression in ovarian and breast cancers (Oh et al.,
1999).
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(5)
Implicated in
Lymphoma oncogene
Note
The MCT-1 oncogene protein modifies mRNA
translational profiles through its interaction with DENR
which contains an SUI1 domain involved in
336
DENR (density-regulated protein)
Reinert LS, Gartenhaus RB
Ovarian cancer and Breast cancer
Oh JJ, Grosshans DR, Wong SG, Slamon DJ. Identification of
differentially expressed genes associated with HER-2/neu
overexpression in human breast cancer cells. Nucleic Acids
Res. 1999 Oct 15;27(20):4008-17
Disease
DENR expression is increased in association with
HER-2 overexpression in ovarian and breast cancers
(Oh. et al., 1999).
Reinert LS, Shi B, Nandi S, Mazan-Mamczarz K, Vitolo M,
Bachman KE, He H, Gartenhaus RB. MCT-1 protein interacts
with the cap complex and modulates messenger RNA
translational profiles. Cancer Res. 2006 Sep 15;66(18):89949001
References
Mazan-Mamczarz K, Gartenhaus RB. Post-transcriptional
control of the MCT-1-associated protein DENR/DRP by RNAbinding protein AUF1. Cancer Genomics Proteomics. 2007
May-Jun;4(3):233-9
recognition of the translation initiation codon (Yoon
and Donahue, 1992; Reinert et.al., 2006).
Yoon HJ, Donahue TF. The suil suppressor locus in
Saccharomyces cerevisiae encodes a translation factor that
functions during tRNA(iMet) recognition of the start codon. Mol
Cell Biol. 1992 Jan;12(1):248-60
This article should be referenced as such:
Reinert LS, Gartenhaus RB. DENR (density-regulated protein).
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(5):336-337.
Deyo JE, Chiao PJ, Tainsky MA. drp, a novel protein
expressed at high cell density but not during growth arrest.
DNA Cell Biol. 1998 May;17(5):437-47
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(5)
337