RNA-binding protein EWS

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. 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. 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.

Interactions

The EWS protein has been shown to interact with:

• ATF1,
• BARD1,
• ERG,
• POU4F1,
• PTK2B
• SF1,
• SNRPC, and
• ZNF165.

References

References

1. (October 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature.
2. "Entrez Gene: EWSR1 Ewing sarcoma breakpoint region 1".
3. (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).
4. "EWS family fusion genes - OMIM".
5. (August 2018). "Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors.". Science.
6. (2012). "Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis". Hum. Mol. Genet..
7. (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.
8. (August 2002). "Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway". Cancer Res..
9. (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.
10. (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..
11. (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol..
12. (July 1998). "The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription". J. Biol. Chem..
13. (August 2000). "The splicing factor U1C represses EWS/FLI-mediated transactivation". J. Biol. Chem..
14. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature.