The AML1/ETO fusion protein activates transcription of BCL-2 Journal Article
| Authors: | Klampfer, L.; Zhang, J.; Zelenetz, A. O.; Uchida, H.; Nimer, S. D. |
| Article Title: | The AML1/ETO fusion protein activates transcription of BCL-2 |
| Abstract: | The AML1 gene, located on chromosome 21, is involved in several distinct chromosomal translocations in human leukemia. In t(8;21) acute myelogenous leukemia (AML), the AML1 gene is juxtaposed to the ETO gene located on chromosome 8, generating an AML1/ETO fusion protein. Both AML1/ETO and the AML1 proteins recognize the same consensus DNA-binding motif (TGT/CGGT), which is found in the promoters of several genes involved in hematopoiesis. We found that two myeloid leukemia cell lines with the t(8;21) translocation, Kasumi and SKNO-1, have elevated levels of BCL-2 protein compared with other myeloid cell lines. In addition, we identified a consensus AML1 binding site in the BCL-2 promoter. Thus far, AML1/ETO has been shown to dominantly repress its target genes; however, we found that AML1/ETO activates transcription of the BCL-2 gene in U937 cells. This activation requires the presence of both the runt homology domain (rhd) and the C-terminal portion of AML1/ETO. We demonstrated sequence specific binding of both AML1A and AML1/ETO to the TGTGGT sequence in the BCL-2 promoter and showed that the AML1 binding site is required for responsiveness to AML1/ETO. Interestingly, AML1A and AML1B do not modulate the activity of the BCL-2 promoter. The elevated levels of BCL-2 in cells that express AML1/ETO may prolong their life span and contribute to the development of 1(8;21) leukemia. |
| Keywords: | controlled study; acute granulocytic leukemia; human cell; promoter region; dna-binding proteins; proto-oncogene proteins; conference paper; protein bcl 2; neoplasm proteins; cell line; transcription factor; chromosomes, human, pair 8; transcription factors; gene activation; blotting, western; hybrid protein; recombinant fusion proteins; gene repression; base sequence; translocation, genetic; binding sites; dna binding; proto-oncogene proteins c-bcl-2; core binding factor alpha 2 subunit; leukemia cell line; chromosome mapping; chromosomes, human, pair 21; consensus sequence; cell strain k 562; chromosome translocation 8; promoter regions (genetics); trans-activation (genetics); leukemia, myelocytic, acute; genes, bcl-2; humans; human; priority journal |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 93 |
| Issue: | 24 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1996-11-26 |
| Start Page: | 14059 |
| End Page: | 14064 |
| Language: | English |
| DOI: | 10.1073/pnas.93.24.14059 |
| PUBMED: | 8943060 |
| PROVIDER: | scopus |
| PMCID: | PMC19494 |
| DOI/URL: | |
| Notes: | Andrew D. Zelenetz's middle initial is incorrect on the original publication -- Conference Paper -- Export Date: 22 November 2017 -- Source: Scopus |
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