Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors
-
Cell Differentiation / genetics
-
DNA-Binding Proteins / chemistry*
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / physiology
-
Disease Models, Animal
-
Humans
-
LIM Domain Proteins
-
Leukemia-Lymphoma, Adult T-Cell / etiology
-
Leukemia-Lymphoma, Adult T-Cell / genetics
-
Metalloproteins / chemistry*
-
Metalloproteins / genetics*
-
Metalloproteins / physiology
-
Mice
-
Mice, Transgenic
-
Oncogenes
-
Phenotype
-
Protein Conformation
-
Proto-Oncogene Proteins*
-
Recombinant Fusion Proteins / chemistry
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / physiology
-
T-Cell Acute Lymphocytic Leukemia Protein 1
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / pathology
-
Thymus Gland / cytology
-
Thymus Gland / growth & development*
-
Transcription Factors*
-
Translocation, Genetic
Substances
-
Adaptor Proteins, Signal Transducing
-
Basic Helix-Loop-Helix Transcription Factors
-
DNA-Binding Proteins
-
LIM Domain Proteins
-
LMO2 protein, human
-
Lmo2 protein, mouse
-
Metalloproteins
-
Proto-Oncogene Proteins
-
Recombinant Fusion Proteins
-
T-Cell Acute Lymphocytic Leukemia Protein 1
-
Tal1 protein, mouse
-
Transcription Factors
-
TAL1 protein, human