The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B Journal Article
| Authors: | Frank, R.; Zhang, J.; Uchida, H.; Meyers, S.; Hiebert, S. W.; Nimer, S. D. |
| Article Title: | The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B |
| Abstract: | The t(8;21) translocation, commonly found in acute myelogenous leukemia (AML), generates a fusion protein containing N-terminal AML1 and C-terminal ETO amino acids. The human AML1 gene encodes several related proteins that specifically bind to the sequence TGT/cGGT, located in the promoter regions of a variety of hematopoietic growth factor genes. To examine the abilities of the AML1B protein (which contains 479 amino acids), a shorter AML1A isoform (which contains amino acids 1-250), and the AML1/ ETO fusion protein (which contains AMLlA amino acids 1-177) to stimulate transcription from the GM-CSF promoter, we performed co-transfection experiments in T cells using a human GM-CSF promoter-CAT reporter gene plasmid and expression vectors that contain the cDNAs for one of the above proteins. Our data demonstrate that AML1B, but not AML1A or AML1/ETO transactivates the GM-CSF promoter, requiring the TGTGGT sequence contained between base pairs -68 and -53. Furthermore, we show that AML1/ETO, but not AML1A, inhibits the ability of AMLlB to stimulate CAT expression. Electrophoretic mobility shift assays demonstrated the specific binding of AML1 proteins to the GM-CSF promoter TGTGGT sequence, which does not require GM-CSF sequences immediately upstream of this binding site. Our data support a role for AML1B as a transcriptional activator and establish that the AML1/ETO fusion protein can act as a dominant negative protein on the human GM-CSF promoter. Although AML1/ETO does not stimulate the transcription of GM-CSF, it may function by inhibiting the normal activity of AML1B in AML cells with the t(8;21) translocation. |
| Keywords: | controlled study; acute granulocytic leukemia; human cell; promoter region; dna-binding proteins; proto-oncogene proteins; nonhuman; animal cell; carboxy terminal sequence; protein dna binding; granulocyte macrophage colony stimulating factor; neoplasm proteins; cell protein; cell line; genetic transcription; transcription factors; molecular sequence data; hybrid protein; amino terminal sequence; genetic transfection; recombinant fusion proteins; transactivation; plasmid; reporter gene; base sequence; binding site; dna sequence; transcriptional activation; receptors, antigen, t-cell, alpha-beta; electrophoretic mobility; complementary dna; core binding factor alpha 2 subunit; hemopoietic growth factor; granulocyte-macrophage colony-stimulating factor; chromosome translocation 8; promoter regions (genetics); trans-activation (genetics); humans; human; priority journal; article; aml1/eto; aml1b; gm-csf promoter |
| Journal Title: | Oncogene |
| Volume: | 11 |
| Issue: | 12 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1995-12-21 |
| Start Page: | 2666 |
| End Page: | 2674 |
| Language: | English |
| PUBMED: | 8545124 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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