| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 2130 |
Name | EWSR1 |
Synonymous | EWS RNA-binding protein 1;EWSR1;EWS RNA-binding protein 1 |
Definition | EWS RNA-binding protein variant 6|Ewing sarcoma breakpoint region 1|Ewings sarcoma EWS-Fli1 (type 1) oncogene|RNA-binding protein EWS |
Position | 22q12.2 |
Gene type | protein-coding |
Title | Abstract |
| EWS/FLI1 suppresses retinoblastoma protein function and senescence in Ewings sarcoma cells. | Ewings Family tumors (EFTs) most commonly harbor a specific t(11;22) translocation that generates the EWS/FLI1 fusion protein responsible for malignant transformation. Many potential downstream targets of EWS/FLI1 have been identified but a detailed mechanism by which the fusion protein brings about transformation remains unknown. In this report, we show that depletion of EWS/FLI1 in Ewings cell lines results in a senescence phenotype, a marked increase in expression of the G1/S regulatory proteins p27(kip1) and p57(kip2), and a significant decrease in cyclin D1 and CDK2. We also demonstrate for the first time, to our knowledge, that knockdown of EWS/FLI1 leads to hypophosphorylation and functional activation of the retinoblastoma (pRb) family of proteins. Consistent with activation of the pRb proteins, E2F-responsive genes such as cyclin A are repressed in EWS/FLI1-depleted cells. Together, these results support the role of EWS/LI1 as an inhibitor of cellular senescence and implicate the retinoblastoma family of proteins as key mediators of this inhibition. |