RNA-binding protein EWS
RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2.[3][4] It is one of 3 proteins in the FET protein family.[5]
| EWSR1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | EWSR1, EWS, bK984G1.4, EWS-FLI1, Ewing sarcoma breakpoint region 1, EWS RNA binding protein 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 133450 HomoloGene: 136069 GeneCards: EWSR1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinical significance
The q22.2 region of chromosome 22 encodes the N-terminal transactivation domain of the EWS protein and that region may become joined to one of several other chromosomes which encode various transcription factors; see EWS/FLI and OMIM-133450.[6] The expression of a chimeric protein with the EWS transactivation domain fused to the DNA binding region of a transcription factor generates a powerful oncogenic protein causing Ewing sarcoma and other members of the Ewing family of tumors. These translocations can occur due to chromoplexy, a burst of complex chromosomal rearrangements seen in cancer cells. [7] The normal EWS gene encodes an RNA binding protein closely related to FUS (gene) and TAF15, all of which have been associated to amyotrophic lateral sclerosis.[8]
Interactions
The EWS protein has been shown to interact with:
References
- GRCh38: Ensembl release 89: ENSG00000182944 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G (October 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature. 359 (6391): 162–5. Bibcode:1992Natur.359..162D. doi:10.1038/359162a0. PMID 1522903. S2CID 4331584.
- "Entrez Gene: EWSR1 Ewing sarcoma breakpoint region 1".
- Flucke U, van Noesel MM, Siozopoulou V, Creytens D, Tops BB, van Gorp JM, Hiemcke-Jiwa LS (June 2021). "EWSR1-The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review". Diagnostics (Basel, Switzerland). 11 (6): 1093. doi:10.3390/diagnostics11061093. PMC 8232650. PMID 34203801.
- "EWS family fusion genes - OMIM".
- Anderson ND, de Borja R, Young MD, Fuligni F, Rosic A, Roberts ND, Hajjar S, Layeghifard M, Novokmet A, Kowalski PE, Anaka M (August 2018). "Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors". Science. 361 (6405): eaam8419. doi:10.1126/science.aam8419. PMC 6176908. PMID 30166462.
- Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD (2012). "Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis". Hum. Mol. Genet. 21 (13): 2899–911. doi:10.1093/hmg/dds116. PMC 3373238. PMID 22454397.
- Fujimura Y, Ohno T, Siddique H, Lee L, Rao VN, Reddy ES (January 1996). "The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator". Oncogene. 12 (1): 159–67. PMID 8552387.
- Spahn L, Petermann R, Siligan C, Schmid JA, Aryee DN, Kovar H (August 2002). "Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway". Cancer Res. 62 (16): 4583–7. PMID 12183411.
- Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, 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.
- Thomas GR, Latchman DS (2002). "The pro-oncoprotein EWS (Ewing's Sarcoma protein) interacts with the Brn-3a POU transcription factor and inhibits its ability to activate transcription". Cancer Biol. Ther. 1 (4): 428–32. doi:10.4161/cbt.1.4.23. PMID 12432261.
- Felsch JS, Lane WS, Peralta EG (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. 9 (9): 485–8. doi:10.1016/s0960-9822(99)80214-0. PMID 10322114.
- Zhang D, Paley AJ, Childs G (July 1998). "The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription". J. Biol. Chem. 273 (29): 18086–91. doi:10.1074/jbc.273.29.18086. PMID 9660765.
- Knoop LL, Baker SJ (August 2000). "The splicing factor U1C represses EWS/FLI-mediated transactivation". J. Biol. Chem. 275 (32): 24865–71. doi:10.1074/jbc.M001661200. PMID 10827180.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Further reading
- Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Res. 53 (24): 5859–63. PMID 7503813.
- Ouchida M, Ohno T, Fujimura Y, Rao VN, Reddy ES (September 1995). "Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts". Oncogene. 11 (6): 1049–54. PMID 7566963.
- Ban J, Siligan C, Kreppel M, Aryee D, Kovar H (2006). "Ews-Fli1 in Ewing's Sarcoma: Real Targets and Collateral Damage". New trends in cancer for the 21st century. Advances in Experimental Medicine and Biology. Vol. 587. pp. 41–52. doi:10.1007/978-1-4020-5133-3_4. ISBN 978-1-4020-4966-8. PMID 17163154.
- Meister HP (1976). "[Morphological findings of chronic constipation in childhood]". Monatsschrift für Kinderheilkunde. 124 (5): 354–6. PMID 934118.
- Guthrie GM, Verstraete A, Deines MM, Stern RM (1975). "Symptoms of stress in four societies". The Journal of Social Psychology. 95 (Second half): 165–72. doi:10.1080/00224545.1975.9918699. PMID 1127890.
- Bhagirath T, Abe S, Nojima T, Yoshida MC (1995). "Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma". Genes Chromosomes Cancer. 13 (2): 126–32. doi:10.1002/gcc.2870130209. PMID 7542907. S2CID 36929552.
- Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, Reddy ES (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.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Plougastel B, Zucman J, Peter M, Thomas G, Delattre O (1994). "Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation". Genomics. 18 (3): 609–15. doi:10.1016/S0888-7543(05)80363-5. PMID 8307570.
- Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CD, Aurias A, Thomas G (1993). "EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts". Nat. Genet. 4 (4): 341–5. doi:10.1038/ng0893-341. PMID 8401579. S2CID 10944105.
- Brodie SG, Stocker SJ, Wardlaw JC, Duncan MH, McConnell TS, Feddersen RM, Williams TM (1996). "EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomen". Hum. Pathol. 26 (12): 1370–4. doi:10.1016/0046-8177(95)90303-8. PMID 8522311.
- Fujimura Y, Ohno T, Siddique H, Lee L, Rao VN, Reddy ES (1996). "The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator". Oncogene. 12 (1): 159–67. PMID 8552387.
- Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS (1996). "Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma". Oncogene. 12 (2): 229–35. PMID 8570200.
- Magnaghi-Jaulin L, Masutani H, Robin P, Lipinski M, Harel-Bellan A (1996). "SRE elements are binding sites for the fusion protein EWS-FLI-1". Nucleic Acids Res. 24 (6): 1052–8. doi:10.1093/nar/24.6.1052. PMC 145748. PMID 8604338.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H, Höglund M, Forster A, Rabbitts TH, Ron D, Mandahl N, Mitelman F (1997). "Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS". Genomics. 37 (1): 1–8. doi:10.1006/geno.1996.0513. PMID 8921363.
- Morohoshi F, Arai K, Takahashi EI, Tanigami A, Ohki M (1997). "Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins". Genomics. 38 (1): 51–7. doi:10.1006/geno.1996.0591. PMID 8954779.
- Zucman-Rossi J, Legoix P, Thomas G (1997). "Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region". Genomics. 38 (3): 247–54. doi:10.1006/geno.1996.0625. PMID 8975699.
- Guinamard R, Fougereau M, Seckinger P (1997). "The SH3 domain of Bruton's tyrosine kinase interacts with Vav, Sam68 and EWS". Scand. J. Immunol. 45 (6): 587–95. doi:10.1046/j.1365-3083.1997.d01-447.x. PMID 9201297.
- Deloulme JC, Prichard L, Delattre O, Storm DR (1997). "The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain". J. Biol. Chem. 272 (43): 27369–77. doi:10.1074/jbc.272.43.27369. PMID 9341188.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
External links
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