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| A repetitive element containing a critical tyrosine residue is required for transcriptional activation by the EWS/ATF1 oncogene |
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| Author(s): Feng L, Lee KAW |
| Source: ONCOGENE Volume: 20 Issue: 31 Pages: 4161-4168 Published: JUL 12 2001 |
| Times Cited: 13 References: 45 |
| Abstract: Chromosomal fusion of the N-terminal region of the Ewings Sarcoma Oncogene (EWS-activation-domain, EAD) to the DNA-binding domains of a variety of cellular transcription factors produce oncogenic proteins (EWS-fusion proteins (EFPs)) that cause distinct malignancies. In EFPs, the EAD acts as a potent transcriptional activation domain and this ability is repressed in the context of normal, non-tumorigenic, EWS, Trans-activation by the EAD is therefore a specific characteristic of EFPs and it is thought that EFPs induce tumorigenesis via improper transcriptional activation of cellular genes. Functional elements required for transcriptional activation are dispersed throughout the EAD, as are thirty-one copies of a Degenerate Hexapeptide Repeat (DHR, consensus SYCQQS), This suggests that the EAD contains a highly reiterated functional element related to DHRs. Here we show that in the context of EWS/ATF1, the EFP that causes malignant melanoma of soft parts, trans-cooperation by small regions of the EAD (similar to 30 residues) results in potent transcriptional activation dependent on the conserved tyrosine residues present in DHRs, These findings provide the first evidence for a role of DHRs in EAD-mediated trans-activation and demonstrate that the EAD represents a novel tyrosine-dependent transcriptional activation domain. |
| Document Type: Article |
| Language: English |
| Reprint Address: Lee, KAW (reprint author), Hong Kong Univ Sci & Technol, Dept Biol, Kowloon, Hong Kong Peoples R China |
Addresses:
1. Hong Kong Univ Sci & Technol, Dept Biol, Kowloon, Hong Kong Peoples R China |
| Publisher: NATURE PUBLISHING GROUP, HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity |
| IDS Number: 452KQ |
| ISSN: 0950-9232 |
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