Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter Journal Article
| Authors: | Uchida, H.; Downing, J. R.; Miyazaki, Y.; Frank, R.; Zhang, J.; Nimer, S. D. |
| Article Title: | Three distinct domains in TEL-AML1 are required for transcriptional repression of the IL-3 promoter |
| Abstract: | A cytogenetically cryptic (12;21) translocation is the most common molecular abnormality identified in childhood acute lymphoblastic leukemia (ALL), and it generates a chimeric TEL-AML1 protein. Fusion of the Helix-Loop-Helix (HLH) (also called the pointed) domain of TEL to AML1 has been suggested to convert AML1 from a transcriptional activator to a repressor. To define the structural features of this chimeric protein required for repression, we analysed the transcriptional activity of a series of TEL-AML1 mutants on the AML1-responsive interleukin-3 (IL-3) promoter, a potentially relevant gene target. Our results demonstrate that TEL-AML1 represses basal IL-3 promoter activity in lymphoid cells, and deletion mutant analysis identified three distinct domains of TEL-AML1 that are required for repression; the HLH (pointed) motif contained in the TEL portion of TEL-AML1, and both the homology domain (Rhd) and the 74 amino downstream of the Rhd that are present in the AML1 portion of the fusion protein. Although AML1B (and a shorter AML1 isoform, AML1A) have transcriptional activating activity on the IL-3 promoter, fusion of the AML1 gene to the TEL gene generates a repressor of IL-3 expression. Consistent with this activity, freshly isolated human ALL cells that contain TEL-AML1 do not express IL-3. |
| Keywords: | child; protein expression; promoter region; neoplasm proteins; genetic transcription; acute lymphoblastic leukemia; gene repression; gene fusion; oncogene proteins, fusion; transcription; translocation, genetic; repressor proteins; core binding factor alpha 2 subunit; chimeric protein; lymphoid cell; repression; helix loop helix protein; interleukin 3; interleukin-3; trans-activation (genetics); leukemia, lymphocytic, acute, l1; humans; priority journal; article; chromosome translocation 12; tel-aml1 |
| Journal Title: | Oncogene |
| Volume: | 18 |
| Issue: | 4 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1999-01-28 |
| Start Page: | 1015 |
| End Page: | 1022 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1202383 |
| PUBMED: | 10023677 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work