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Download Gene Section DENR (density-regulated protein) Atlas of Genetics and Cytogenetics
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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