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Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene

Abstract

THE Ets-1 proto-oncogene is a member of a transcription factor family characterized by homology to the v-ets oncogene1á¤-4. In adult mice, Ets-1 is expressed predominantly in lymphoid cells where it has been implicated in regulating transcription of lymphocyte-specific genes5á¤-7. Following T-cell activation, the specific DNA binding activity of Ets-1 is inactivated by transient phosphoryla-tion, suggesting a function in the transition from the resting to activated state8,9. Ets-1 has also been suggested to cooperate with the AP-1 transcription factor complex to mediate cellular growth factor responses4. Here we show, by using RAG-2-deficient blasto-cyst complementation10, that Ets-1 deficiency has dramatic, but different, effects on development and function of T- and B-lineage cells. Ets-1-deficient T cells were present in reduced numbers and were highly susceptible to cell death in vitro. In contrast, Ets-1-deficient B cells were present in normal numbers but a large proportion were IgM plasma cells. Our data demonstrate that Ets-1 is essential for maintenance of the normal pool of resting T- and B-lineage cells.

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Bories, JC., Willerford, D., Grévin, D. et al. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene. Nature 377, 635–638 (1995). https://doi.org/10.1038/377635a0

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