Document Detail

c-Myb regulates the proliferation of immature thymocytes following beta-selection.
MedLine Citation:
PMID:  11080157     Owner:  NLM     Status:  MEDLINE    
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.
R Pearson; K Weston
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The EMBO journal     Volume:  19     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-15     Completed Date:  2001-01-04     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  6112-20     Citation Subset:  IM    
CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
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MeSH Terms
Antigens, CD4 / metabolism
Antigens, CD8 / metabolism
Base Sequence
Cell Cycle
Cell Differentiation
Cell Division
DNA Primers / genetics
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Genes, myb
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-myb / metabolism*
Proto-Oncogene Proteins c-pim-1
T-Lymphocytes / cytology*,  immunology,  metabolism*
Reg. No./Substance:
0/Antigens, CD4; 0/Antigens, CD8; 0/DNA Primers; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-myb; EC protein, mouse; EC Kinases; EC Proteins c-pim-1

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