Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice.
The LMO2 and TAL1 genes were first identified via chromosomal translocations and later found to encode proteins that interact during normal erythroid development. Some T cell leukaemia patients have chromosomal abnormalities involving both genes, implying that LMO2 and TAL1 act synergistically to promote tumorigenesis after their inappropriate co-expression. To test this hypothesis, transgenic mice were made which co-express Lmo2 and Tal1 genes in T cells. Dimers of Lmo2 and Tal1 proteins were formed in thymocytes of double but not single transgenic mice. Furthermore, thymuses of double transgenic mice were almost completely populated by immature T cells from birth, and these mice develop T cell tumours approximately 3 months earlier than those with only the Lmo2 transgene. Thus interaction between these two proteins can alter T cell development and potentiate tumorigenesis. The data also provide formal proof that TAL1 is an oncogene, apparently acting as a tumour promoter in this system.
Larson
R C
RC
MRC Laboratory of Molecular Biology, Cambridge, UK.
Lavenir
I
I
Larson
T A
TA
Baer
R
R
Warren
A J
AJ
Wadman
I
I
Nottage
K
K
Rabbitts
T H
TH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000235:genetics; D008667:Metalloproteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D010641:Phenotype; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development*; D014157:Transcription Factors; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human