The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology; Department of Cancer Biology
Medical Subject Headings
Adenovirus E2 Proteins; Animals; Antigens, CD4; Basic Helix-Loop-Helix Transcription Factors; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Casein Kinase II; Cell Differentiation; DNA; DNA-Binding Proteins; Dimerization; Disease Models, Animal; *Helix-Loop-Helix Motifs; Humans; Leukemia-Lymphoma, Adult T-Cell; Lymphoma; Metalloproteins; Mice; Mice, Transgenic; Mutagenesis; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; TCF Transcription Factors; Thymoma; Thymus Gland; Thymus Neoplasms; Transcription Factors
Life Sciences | Medicine and Health Sciences
Activation of the basic helix-loop-helix (bHLH) gene TAL-1 (or SCL) is the most frequent gain-of-function mutation in pediatric T cell acute lymphoblastic leukemia (T-ALL). Similarly, mis-expression of tal-1 in the thymus of transgenic mice results in the development of clonal T cell lymphoblastic leukemia. To determine the mechanism(s) of tal-1-induced leukemogenesis, we created transgenic mice expressing a DNA binding mutant of tal-1. Surprisingly, these mice develop disease, demonstrating that the DNA binding properties of tal-1 are not required to induce leukemia/lymphoma in mice. However, wild type tal-1 and the DNA binding mutant both form stable complexes with E2A proteins. In addition, tal-1 stimulates differentiation of CD8-single positive thymocytes but inhibits the development of CD4-single positive cells: effects also observed in E2A-deficient mice. Our study suggests that the bHLH protein tal-1 contributes to leukemia by interfering with E2A protein function(s).
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Citation: Oncogene. 2001 Jun 28;20(29):3897-905. Link to article on publisher's site
O'Neil, Jennifer Elinor; Billa, Marilisa; Oikemus, Sarah R.; and Kelliher, Michelle, "The DNA binding activity of TAL-1 is not required to induce leukemia/lymphoma in mice" (2001). GSBS Student Publications. 912.