ERG (gene)
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| V-ets erythroblastosis virus E26 oncogene homolog (avian) | |||||||||||||
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 PDB rendering based on 1fli. |
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| Identifiers | |||||||||||||
| Symbols | ERG; erg-3; p55 | ||||||||||||
| External IDs | OMIM: 165080 MGI: 95415 HomoloGene: 15848 GeneCards: ERG Gene | ||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 2078 | 13876 | |||||||||||
| Ensembl | ENSG00000157554 | ENSMUSG00000040732 | |||||||||||
| UniProt | P11308 | Q3UQJ4 | |||||||||||
| RefSeq (mRNA) | NM_001136154.1 | NM_133659.2 | |||||||||||
| RefSeq (protein) | NP_001129626.1 | NP_598420.1 | |||||||||||
| Location (UCSC) | Chr 21: 39.75 – 40.03 Mb |
Chr 16: 95.58 – 95.81 Mb |
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| PubMed search | [1] | [2] | |||||||||||
Transcriptional regulator ERG is a protein that in humans is encoded by the ERG gene (Ets Related Gene).[1][2][3][4] ERG is a member of the ETS family of transcription factors.
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[edit] Function
Transcriptional regulator ERG is a nuclear protein that binds purine-rich sequences.[5][6] ERG is expressed at higher levels in early myelocytes than in mature lymphocytes. Therefore ERG may act as a regulator of differentiation of early hematopoietic cells.[7] Erg gene is vitally important to blood stem cells' unique ability to self-renew could give scientists new opportunities to use blood stem cells for tissue repair, transplantation and other therapeutic applications.[8]
The Mld2 mutation generated through an ENU mutagenesis screen, was the first non-functional allele of Erg. Homozygous Mld2 is embryonic lethal at day 13.5. Adult mice heterozygous for the Mld2 mutation have hematopoietic stem cell defects. [9] DNA binding protein ERG fuses with RNA binding proteins EWS and TLS/FUS in Ewing Sarcoma and Acute Myeloid Leukemias respectively and function as transcriptional activators. [10][11]. ERG and it's fusion proteins EWS-ERG and TLS/FUS-ERG inhibit apoptosis. [12]
[edit] TMPRSS2 gene fusion
ERG can fuse with TMPRSS2 protein to form an oncogenic fusion gene that is commonly found in human prostate cancer, especially in hormone-refractory prostate cancer. This suggests that ERG overexpression may contribute to development of androgen-independence in prostate cancer through disruption of androgen receptor signaling.[13]
[edit] Interactions
ERG (gene) has been shown to interact with:
[edit] References
- ^ Reddy ES, Rao VN, Papas TS (September 1987). "The erg gene: a human gene related to the ets oncogene". Proc. Natl. Acad. Sci. U.S.A. 84 (17): 6131–5. doi:10.1073/pnas.84.17.6131. PMC 299022. PMID 3476934. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299022.
- ^ Rao VN, Papas TS, Reddy ES (1987). "erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation". Science 237 (4815): 635–9. doi:10.1126/science.3299708. PMID 3299708.
- ^ Rao VN, Modi WS, Drabkin HD, Patterson D, O'Brien SJ, Papas TS, Reddy ES (November 1988). "The human erg gene maps to chromosome 21, band q22: relationship to the 8; 21 translocation of acute myelogenous leukemia". Oncogene 3 (5): 497–500. PMID 3274086.
- ^ "Entrez Gene: ERG v-ets erythroblastosis virus E26 oncogene homolog (avian)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2078.
- ^ Reddy ES, Rao VN (December 1991). "erg, an ets-related gene, codes for sequence-specific transcriptional activators". Oncogene 6 (12): 2285–9. PMID 1766675.}}
- ^ Siddique HR, Rao VN, Lee L, Reddy ES (July 1993). "Characterization of the DNA binding and transcriptional activation domains of the erg protein". Oncogene 8 (7): 1751–5. PMID 8510921.
- ^ Murakami K, Mavrothalassitis G, Bhat NK, Fisher RJ, Papas TS (June 1993). "Human ERG-2 protein is a phosphorylated DNA-binding protein--a distinct member of the ets family". Oncogene 8 (6): 1559–66. PMID 8502479.
- ^ 1.S. Taoudi, T. Bee, A. Hilton, K. Knezevic, J. Scott, T. A. Willson, C. Collin, T. Thomas, A. K. Voss, B. T. Kile, W. S. Alexander, J. E. Pimanda, D. J. Hilton (Feb 2011). "ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification". Genes & Development 825 (3): 251–262. doi:10.1101/gad.2009211. PMC 3034900. PMID 21245161. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3034900.
- ^ Nature Immunology 9, 810 - 819 (2008) The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells Stephen J Loughran, Elizabeth A Kruse, Douglas F Hacking, Carolyn A de Graaf, Craig D Hyland, Tracy A Willson, Katya J Henley, Sarah Ellis, Anne K Voss, Donald Metcalf, Douglas J Hilton Warren S Alexander & Benjamin T Kile
- ^ a b Ohno T, Ouchida M, Lee L, Gatalica Z, Rao, VN and Reddy, ES (oct 1994). "The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains". Oncogene 9 (10): 3087–97. PMID 8084618.
- ^ a b Prasad, DDK, Ouchida, M, Lee, L, Rao, VN and Reddy, ES (dec 1994). "TLS/FUS fusion domain of TLS/FUS‑erg chimeric protein resulting from the t(16;21) chromosome translocation in human myeloid leukemia functions as a transcriptional activation domain". Oncogene 9 (12): 3717–29. PMID 7970732.
- ^ Yi H, Fujimura Y, Ouchida M, Prasad DD, Rao VN, Reddy ES (March 1997). "Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias". Oncogene 14 (11): 1259–68. doi:10.1038/sj.onc.1201099. PMID 9178886.
- ^ a b Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM (May 2010). "An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression". Cancer Cell 17 (5): 443–54. doi:10.1016/j.ccr.2010.03.018. PMC 2874722. PMID 20478527. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2874722.
- ^ Verger A, Buisine E, Carrère S, Wintjens R, Flourens A, Coll J, Stéhelin D, Duterque-Coquillaud M (May 2001). "Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation". J. Biol. Chem. 276 (20): 17181–9. doi:10.1074/jbc.M010208200. PMID 11278640.
- ^ Basuyaux JP, Ferreira E, Stéhelin D, Butticè G (October 1997). "The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA-dependent and -independent manner". J. Biol. Chem. 272 (42): 26188–95. doi:10.1074/jbc.272.42.26188. PMID 9334186.
[edit] Further reading
- Yi H, Fujimura Y, Ouchida M, Prasad DD, Rao VN, Reddy ES (March 1997). "Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias". Oncogene 14 (11): 1259–68. doi:10.1038/sj.onc.1201099. PMID 9178886.
- Rao VN, Papas TS, Reddy ES (1987). "erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation". Science 237 (4815): 635–9. doi:10.1126/science.3299708. PMID 3299708.
- Giovannini M, Biegel JA, Serra M et al (1994). "EWS-erg and EWS-Fli1 fusion transcripts in Ewing's sarcoma and primitive neuroectodermal tumors with variant translocations". J. Clin. Invest. 94 (2): 489–96. doi:10.1172/JCI117360. PMC 295111. PMID 8040301. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=295111.
- Dunn T, Praissman L, Hagag N, Viola MV (1994). "ERG gene is translocated in an Ewing's sarcoma cell line". Cancer Genet. Cytogenet. 76 (1): 19–22. doi:10.1016/0165-4608(94)90063-9. PMID 8076344.
- Ichikawa H, Shimizu K, Hayashi Y, Ohki M (1994). "An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation". Cancer Res. 54 (11): 2865–8. PMID 8187069.
- Prasad DD, Rao VN, Lee L, Reddy ES (1994). "Differentially spliced erg-3 product functions as a transcriptional activator". Oncogene 9 (2): 669–73. PMID 8290279.
- Duterque-Coquillaud M, Niel C, Plaza S, Stehelin D (1993). "New human erg isoforms generated by alternative splicing are transcriptional activators". Oncogene 8 (7): 1865–73. PMID 8510931.
- Basuyaux JP, Ferreira E, Stéhelin D, Butticè G (1997). "The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA-dependent and -independent manner". J. Biol. Chem. 272 (42): 26188–95. doi:10.1074/jbc.272.42.26188. PMID 9334186.
- Carrère S, Verger A, Flourens A et al (1998). "Erg proteins, transcription factors of the Ets family, form homo, heterodimers and ternary complexes via two distinct domains". Oncogene 16 (25): 3261–8. doi:10.1038/sj.onc.1201868. PMID 9681824.
- McLaughlin F, Ludbrook VJ, Kola I et al (2000). "Characterisation of the tumour necrosis factor (TNF)-(alpha) response elements in the human ICAM-2 promoter". J. Cell. Sci. 112 (24): 4695–703. PMID 10574717.
- Hattori M, Fujiyama A, Taylor TD et al (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
- Mastrangelo T, Modena P, Tornielli S et al (2000). "A novel zinc finger gene is fused to EWS in small round cell tumor". Oncogene 19 (33): 3799–804. doi:10.1038/sj.onc.1203762. PMID 10949935.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310948.
- Verger A, Buisine E, Carrère S et al (2001). "Identification of amino acid residues in the ETS transcription factor Erg that mediate Erg-Jun/Fos-DNA ternary complex formation". J. Biol. Chem. 276 (20): 17181–9. doi:10.1074/jbc.M010208200. PMID 11278640.
- Yang L, Xia L, Wu DY et al (2002). "Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor". Oncogene 21 (1): 148–52. doi:10.1038/sj.onc.1204998. PMID 11791185.
- Mackereth CD, Schärpf M, Gentile LN, McIntosh LP (2003). "Chemical shift and secondary structure conservation of the PNT/SAM domains from the ets family of transcription factors". J. Biomol. NMR 24 (1): 71–2. doi:10.1023/A:1020617426325. PMID 12449421.
- Strausberg RL, Feingold EA, Grouse LH et al (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Matsui Y, Chansky HA, Barahmand-Pour F et al (2003). "COL11A2 collagen gene transcription is differentially regulated by EWS/ERG sarcoma fusion protein and wild-type ERG". J. Biol. Chem. 278 (13): 11369–75. doi:10.1074/jbc.M300164200. PMID 12554743.
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