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Publication : c-Myb regulates the proliferation of immature thymocytes following beta-selection.

First Author  Pearson R Year  2000
Journal  EMBO J Volume  19
Issue  22 Pages  6112-20
PubMed ID  11080157 Mgi Jnum  J:115111
Mgi Id  MGI:3690681 Doi  10.1093/emboj/19.22.6112
Citation  Pearson R, et al. (2000) c-Myb regulates the proliferation of immature thymocytes following beta-selection. EMBO J 19(22):6112-20
abstractText  Transgenic mice expressing a T-cell-specific dominant interfering allele (MEnT) of the c-Myb transcription factor have a pronounced block in CD4(-)CD8(-) (DN) development. In this study we show that differentiation of DN MEnT thymocytes is blocked due to the failure of cells to enter the cell cycle following beta-selection, the process by which productive rearrangement of the T-cell receptor (TCR) beta-chain permits maturation of cells into CD4(+)CD8(+) (DP) thymocytes. c-myb mRNA continues to be expressed in DN cells in mice lacking a functional pre-TCR signalling pathway, implying that its transcriptional regulation is independent of the signalling events regulating beta-selection. It is also expressed in the absence of cytokine signalling. However, we show that c-Myb protein is required for the function in beta-selection of its known upstream activator, the serine/threonine kinase Pim1: MEnT expression inhibits the cell cycle in Pim1 transgenic DN thymocytes and prevents Pim1-mediated rescue of a RAG1(-/-) developmental block. Super activation of c-Myb by Pim1 may therefore be required for beta-selection.
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