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J Biol Chem. 2012 Feb 17;287(8):5199-210. doi: 10.1074/jbc.M111.242602. Epub 2011 Nov 29.

Role for Ets-2(Thr-72) transcription factor in stage-specific thymocyte development and survival.

Author information

1
Molecular Cellular Developmental Biology Program, Division of Hematology, Ohio State University, Columbus, Ohio 43210, USA.

Abstract

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.

PMID:
22128184
PMCID:
PMC3285301
DOI:
10.1074/jbc.M111.242602
[Indexed for MEDLINE]
Free PMC Article
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