The basic helix-loop-helix transcription factor TAL1/SCL inhibits the expression of the p16INK4A and pTalpha genes.
The Tal1 gene (also called Scl or TCL5) encodes a basic helix-loop-helix transcription factor required for hematopoiesis and vasculogenesis. Additionally, aberrant transcriptional activation of the Tal1 gene is a frequent event in human T cell acute lymphoblastic leukemia (T-ALL). T cell specific expression of TAL1 in mice induces aggressive T cell malignancies, demonstrating the oncogenic potential of TAL1. Yet, the underlying mechanisms of TAL1 induced tumorigenesis are poorly understood. By inhibiting E protein mediated transcription of the pTalpha gene, TAL1 can interfere with the T cell differentiation program. In addition, several studies suggest that TAL1 expression might also enhance proliferation rate. We report here that TAL1 can bind the E boxes in both the p16 and the pTalpha promoters, and functionally suppress the activity of both promoters. These results indicate that TAL1 can affect both T cell proliferation and differentiation. Moreover, we show that overexpression of TAL1 in hematopoietic progenitor cells promotes cell cycle division.
Hansson
Anders
A
Department of Laboratory Medicine, Division of Molecular Medicine, Lund University, University Hospital MAS, SE-205 02, Malmö, Sweden.
Manetopoulos
Christina
C
Jönsson
Jan Ingvar
JI
Axelson
Håkan
H
D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000502:physiology*; D019942:Genes, p16 / Q000502:physiology; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C090377:pre-T cell receptor alpha; C067143:TAL1 protein, human