The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells.
The LIM-only protein LMO2 is expressed aberrantly in acute T-cell leukaemias as a result of the chromosomal translocations t(11;14) (p13;q11) or t(7;11) (q35;p13). In a transgenic model of tumorigenesis by Lmo2, T-cell acute leukaemias arise after an asymptomatic phase in which an accumulation of immature CD4(-) CD8(-) double negative thymocytes occurs. Possible molecular mechanisms underlying these effects have been investigated in T cells from Lmo2 transgenic mice. Isolation of DNA-binding sites by CASTing and band shift assays demonstrates the presence of an oligomeric complex involving Lmo2 which can bind to a bipartite DNA motif comprising two E-box sequences approximately 10 bp apart, which is distinct from that found in erythroid cells. This complex occurs in T-cell tumours and it is restricted to the immature CD4(- )CD8(-) thymocyte subset in asymptomatic transgenic mice. Thus, ectopic expression of Lmo2 by transgenesis, or by chromosomal translocations in humans, may result in the aberrant protein interactions causing abnormal regulation of gene expression, resulting in a blockage of T-cell differentiation and providing precursor cells for overt tumour formation.
Grütz
G G
GG
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Bucher
K
K
Lavenir
I
I
Larson
T
T
Larson
R
R
Rabbitts
T H
TH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D007106:Immune Sera; D060588:LIM Domain Proteins; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology; D008667:Metalloproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D007106:Immune Sera; D060588:LIM Domain Proteins; C513188:Lmo2 protein, mouse; D008667:Metalloproteins; D009838:Oligodeoxyribonucleotides