Biology:RNA-binding protein EWS

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Short description: Human protein and coding gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2.[1][2] It is one of 3 proteins in the FET protein family.[3]

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.[4] 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. [5] 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.[6]

Interactions

The EWS protein has been shown to interact with:

References

  1. ↑ "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature 359 (6391): 162–5. October 1992. doi:10.1038/359162a0. PMID 1522903. Bibcode: 1992Natur.359..162D. 
  2. ↑ "Entrez Gene: EWSR1 Ewing sarcoma breakpoint region 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2130. 
  3. ↑ "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. June 2021. doi:10.3390/diagnostics11061093. PMID 34203801. 
  4. ↑ "EWS family fusion genes - OMIM". http://omim.org/entry/133450. 
  5. ↑ "Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors.". Science 361 (6405): eaam8419. August 2018. doi:10.1126/science.aam8419. PMID 30166462. 
  6. ↑ "Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis". Hum. Mol. Genet. 21 (13): 2899–911. 2012. doi:10.1093/hmg/dds116. PMID 22454397. 
  7. ↑ "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. January 1996. PMID 8552387. 
  8. ↑ "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. August 2002. PMID 12183411. 
  9. ↑ "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. Oct 1994. PMID 8084618. 
  10. ↑ "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. 2002. doi:10.4161/cbt.1.4.23. PMID 12432261. 
  11. ↑ "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. 9 (9): 485–8. May 1999. doi:10.1016/s0960-9822(99)80214-0. PMID 10322114. 
  12. ↑ "The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription". J. Biol. Chem. 273 (29): 18086–91. July 1998. doi:10.1074/jbc.273.29.18086. PMID 9660765. 
  13. ↑ "The splicing factor U1C represses EWS/FLI-mediated transactivation". J. Biol. Chem. 275 (32): 24865–71. August 2000. doi:10.1074/jbc.M001661200. PMID 10827180. 
  14. ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R. 

Further reading

  • "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Res. 53 (24): 5859–63. December 1993. PMID 7503813. 
  • "Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts". Oncogene 11 (6): 1049–54. September 1995. PMID 7566963. 
  • "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. 587. 2006. pp. 41–52. doi:10.1007/978-1-4020-5133-3_4. ISBN 978-1-4020-4966-8. 
  • "[Morphological findings of chronic constipation in childhood]". Monatsschrift für Kinderheilkunde 124 (5): 354–6. 1976. PMID 934118. 
  • "Symptoms of stress in four societies". The Journal of Social Psychology 95 (Second half): 165–72. 1975. doi:10.1080/00224545.1975.9918699. PMID 1127890. 
  • "Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma". Genes Chromosomes Cancer 13 (2): 126–32. 1995. doi:10.1002/gcc.2870130209. PMID 7542907. 
  • "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. 1994. PMID 8084618. 
  • "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • "Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation". Genomics 18 (3): 609–15. 1994. doi:10.1016/S0888-7543(05)80363-5. PMID 8307570. 
  • "EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts". Nat. Genet. 4 (4): 341–5. 1993. doi:10.1038/ng0893-341. PMID 8401579. 
  • "EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomen". Hum. Pathol. 26 (12): 1370–4. 1996. doi:10.1016/0046-8177(95)90303-8. PMID 8522311. 
  • "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. 1996. PMID 8552387. 
  • "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. 1996. PMID 8570200. 
  • "SRE elements are binding sites for the fusion protein EWS-FLI-1". Nucleic Acids Res. 24 (6): 1052–8. 1996. doi:10.1093/nar/24.6.1052. PMID 8604338. 
  • "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. 1997. doi:10.1101/gr.6.9.791. PMID 8889548. 
  • "Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS". Genomics 37 (1): 1–8. 1997. doi:10.1006/geno.1996.0513. PMID 8921363. 
  • "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. 1997. doi:10.1006/geno.1996.0591. PMID 8954779. 
  • "Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region". Genomics 38 (3): 247–54. 1997. doi:10.1006/geno.1996.0625. PMID 8975699. 
  • "The SH3 domain of Bruton's tyrosine kinase interacts with Vav, Sam68 and EWS". Scand. J. Immunol. 45 (6): 587–95. 1997. doi:10.1046/j.1365-3083.1997.d01-447.x. PMID 9201297. 
  • "The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain". J. Biol. Chem. 272 (43): 27369–77. 1997. doi:10.1074/jbc.272.43.27369. PMID 9341188. 
  • "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 

External links



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