Tyrosine phosphorylation is required for up-regulation of the HOX-11 (TCL-3) homeobox proto-oncogene in T cells.
HOX-11 (TCL-3) is a homeobox proto-oncogene isolated from the breakpoint region of the t(10;14) chromosomal translocation associated with pediatric T-cell acute leukemia. To better understand the transcriptional regulation of the HOX-11 gene in response to extracellular signals, the levels of HOX-11 RNA were examined in normal and leukemic human T cells upon phytohemagglutinin and hematopoietic growth factor stimulation. While individual hematopoietic growth factors tested did not show any effect on HOX-11 gene expression, a drastic increase in HOX-11 RNA was observed under the induction of phytohemagglutinin. In the presence of cycloheximide, a protein synthesis inhibitor, phytohemagglutinin-induced HOX-11 up-regulation was suppressed, indicating that HOX-11 acts as a delayed early response gene which requires protein synthesis. The HOX-11 gene expression was also suppressed by the tyrosine kinase inhibitors tryphostin and lavendustin A. Our data therefore suggest that the delayed early response of HOX-11 up-regulation in T cells requires a tyrosine phosphorylation signal.
Zhang
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Cancer Center, University of California at San Diego 92103-8421.
Shen
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D001483:Base Sequence; D005786:Gene Expression Regulation / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D005801:Genes, Homeobox; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D010835:Phytohemagglutinins; D000090063:Proto-Oncogene Mas; D014443:Tyrosine