RNA Helicase Promotes Growth of Ewing's Sarcoma

This cancer develops as the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11. The fused genes produce the EWS-FLI1 fusion protein, which is only found in Ewing's sarcoma tumors.

Investigators at Georgetown University (Washington, DC, USA) sought co-factor proteins that might modulate the activity of EWS-FLI1 in order to find a means of chemically blocking this interaction and thereby slowing or stopping tumor growth.

They reported in the June 1, 2006, issue of Cancer Research that EWS-FLI1 specifically binds an RNA helicase A (RHA) peptide fragment comprising amino acids 630 to 1020. RHA is a member of the DEXH box helicase family of proteins, and is an integral component of protein complexes that regulate transcription and splicing.

"Proteins are three-dimensional structures, and the space between EWS-FLI1 and the helicase might be targetable by a small molecule that keeps the proteins apart,” explained first author Dr. Jeffrey Toretsky, associate professor of oncology and pediatrics at Georgetown University. "It could render EWS-FLI1 harmless while not affecting its partnering helicase protein. Understanding the molecules EWS-FLI1 interacts with may provide insights into similar diseases. Very little work has been done to study the functional partners of these translocation proteins, and this study may offer a new research approach.”



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