| First Author | Fukuda S | Year | 2004 |
| Journal | Biochem Biophys Res Commun | Volume | 323 |
| Issue | 2 | Pages | 636-44 |
| PubMed ID | 15369798 | Mgi Jnum | J:92477 |
| Mgi Id | MGI:3052889 | Doi | 10.1016/j.bbrc.2004.08.149 |
| Citation | Fukuda S, et al. (2004) Activated H-Ras regulates hematopoietic cell survival by modulating Survivin. Biochem Biophys Res Commun 323(2):636-44 |
| abstractText | Survivin expression and Ras activation are regulated by hematopoietic growth factors. We investigated whether activated Ras could circumvent growth factor-regulated Survivin expression and if a Ras/Survivin axis mediates growth factor independent survival and proliferation in hematopoietic cells. Survivin expression is up-regulated by IL-3 in Ba/F3 and CD34(+) cells and inhibited by the Ras inhibitor, farnesylthiosalicylic acid. Over-expression of constitutively activated H-Ras (CA-Ras) in Ba/F3 cells blocked down-modulation of Survivin expression, G(0)/G(1) arrest, and apoptosis induced by IL-3 withdrawal, while dominant-negative (DN) H-Ras down-regulated Survivin. Survivin disruption by DN T34A Survivin blocked CA-Ras-induced IL-3-independent cell survival and proliferation; however, it did not affect CA-Ras-mediated enhancement of S-phase, indicating that the anti-apoptotic activity of CA-Ras is Survivin dependent while its S-phase enhancing effect is not. These results indicate that CA-Ras modulates Survivin expression independent of hematopoietic growth factors and that a CA-Ras/Survivin axis regulates survival and proliferation of transformed hematopoietic cells. |
