title: Role for Ets-2(Thr-72) transcription factor in stage-specific thymocyte development and survival.
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.
authors: Molecular Cellular Developmental Biology Program, Division of Hematology, Ohio State University, Columbus, Ohio 43210, USA.
authors: Ian B
authors: IB
authors: Fisher
authors: Mike
authors: M
authors: Ostrowski
authors: Natarajan
authors: N
authors: Muthusamy
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002452:Cell Count; D049109:Cell Proliferation; D048429:Cell Size; D002470:Cell Survival / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010766:Phosphorylation; D055503:Protein Multimerization / Q000235:genetics; D020836:Protein Structure, Quaternary; D050787:Proto-Oncogene Protein c-ets-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013912:Threonine / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D050787:Proto-Oncogene Protein c-ets-2; D019253:Proto-Oncogene Proteins c-bcl-2; D013912:Threonine; D019009:Proto-Oncogene Proteins c-kit; D018631:ras Proteins