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| The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B |
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| Author(s): Frank R, Zhang J, Uchida H, Meyers S, Hiebert SW, Nimer SD |
| Source: ONCOGENE Volume: 11 Issue: 12 Pages: 2667-2674 Published: DEC 21 1995 |
| Times Cited: 164 References: 48 |
| Abstract: The t(8;21) translocation, commonly found myelogenous leukemia (AML), generates 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 AML1A amino acids 1-177) to stimulate transcription from the GMCSF 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 AML1B 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 GMCSF 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. MEM SLOAN KETTERING CANC CTR, SLOAN KETTERING INST, LAB MOLEC ASPECTS HEMATOPOIESIS, NEW YORK, NY 10021 USA
2. MEM SLOAN KETTERING CANC CTR, DEPT MED, DIV HEMATOL ONCOL, NEW YORK, NY 10021 USA
3. ST JUDE CHILDRENS HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA |
| Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS |
| Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity |
| IDS Number: TP188 |
| ISSN: 0950-9232 |
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