First Author | Fisher IB | Year | 2012 |
Journal | J Biol Chem | Volume | 287 |
Issue | 8 | Pages | 5199-210 |
PubMed ID | 22128184 | Mgi Jnum | J:182468 |
Mgi Id | MGI:5315671 | Doi | 10.1074/jbc.M111.242602 |
Citation | Fisher IB, et al. (2012) Role for Ets-2(Thr-72) transcription factor in stage-specific thymocyte development and survival. J Biol Chem 287(8):5199-210 |
abstractText | Interference of Ras signaling deregulates thymocyte development in mouse models. However, the role of Ets-2, a transcription factor that is phosphorylated on a critical threonine residue (Thr-72) by the Ras/MAPK pathway in thymocyte development, has not been defined. Transgenic mice overexpressing a phosphomutant Ets-2 (T72A) in the thymus displayed reduced thymus size associated with a 60-80% reduction in thymocyte populations. The transgenic mice exhibited a 20-fold increase in a c-Kit(+) CD4(+) CD8(+) CD3(-) population and a 5-fold increase in a unique CD5(low) population associated with a partial developmental block at the DN2-DN3 stage of thymocytes. Transgenic thymocytes exhibited increased apoptosis, and overexpression of Bcl-2 rescued the hypocellularity and associated thymocyte developmental block in double transgenic mice. The observed defects in these mice are not dependent on Ets-1 expression. These studies implicate for the first time a stage-specific Ets-1-independent regulatory role for Ets-2 in early thymocyte development and survival. |