Abstract
The product of the scl (also called tal-1 or TCL5) gene is a basic domain, helix-loop-helix (bHLH) transcription factor required for the development of hematopoietic cells. Additionally, scl gene disruption and dysregulation, by either chromosomal translocations or a site-specific interstitial deletion whereby 5' regulatory elements of the sil gene become juxtaposed to the body of the scl gene, is associated with T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma. Here we show that an inappropriately expressed scl protein, driven by sil regulatory elements, can cause aggressive T-cell malignancies in collaboration with a misexpressed LMO1 protein, thus recapitulating the situation seen in a subset of human T-cell ALL. Moreover, we show that inappropriately expressed scl can interfere with the development of other tissues derived from mesoderm. Lastly, we show that an scl construct lacking the scl transactivation domain collaborates with misexpressed LMO1, demonstrating that the scl transactivation domain is dispensable for oncogenesis, and supporting the hypothesis that the scl gene product exerts its oncogenic action through a dominant-negative mechanism.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors
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Binding Sites
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Bone and Bones / abnormalities*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Exons
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Genetic Vectors
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Helix-Loop-Helix Motifs
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Humans
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LIM Domain Proteins
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Leukemia-Lymphoma, Adult T-Cell / genetics*
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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Metalloproteins / chemistry
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Metalloproteins / metabolism*
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Nuclear Proteins
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Oncogene Proteins*
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Oncogene Proteins, Fusion*
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Phenotype
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Protein Serine-Threonine Kinases
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Proteins / genetics
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Proteins / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-pim-1
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Recombination, Genetic
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
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Tumor Cells, Cultured
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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LIM Domain Proteins
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LMO1 protein, human
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Lmo1 protein, mouse
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Metalloproteins
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Nuclear Proteins
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Oncogene Proteins
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Oncogene Proteins, Fusion
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Proteins
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Proto-Oncogene Proteins
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SIL protein, mouse
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Tal1 protein, mouse
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Transcription Factors
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TAL1 protein, human
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PIM1 protein, human
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Pim1 protein, mouse
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-pim-1
Associated data
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GENBANK/L76150
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GENBANK/M26682