PUBLICATION
The elongation factor ELL (Eleven-Nineteen Lysine-Rich Leukemia) acts as a transcription factor for direct thrombospondin-1 regulation
- Authors
- Zhou, J., Feng, X., Ban, B., Liu, J., Wang, Z., and Xiao, W.
- ID
- ZDB-PUB-090526-6
- Date
- 2009
- Source
- The Journal of biological chemistry 284(28): 19142-19152 (Journal)
- Registered Authors
- Xiao, Wuhan
- Keywords
- TRANSCRIPTION, ELL, Eaf1, MLL, TSP-1, U19/Eaf2, p53, transcription factor
- MeSH Terms
-
- Animals
- Base Sequence
- Gene Deletion
- Gene Expression Regulation*
- Gene Expression Regulation, Leukemic*
- Humans
- In Situ Hybridization
- Leukemia/metabolism*
- Models, Biological
- Molecular Sequence Data
- Mutation
- Protein Structure, Tertiary
- Thrombospondin 1/biosynthesis*
- Transcriptional Activation
- Transcriptional Elongation Factors/metabolism*
- Transcriptional Elongation Factors/physiology*
- Zebrafish
- PubMed
- 19447890 Full text @ J. Biol. Chem.
Citation
Zhou, J., Feng, X., Ban, B., Liu, J., Wang, Z., and Xiao, W. (2009) The elongation factor ELL (Eleven-Nineteen Lysine-Rich Leukemia) acts as a transcription factor for direct thrombospondin-1 regulation. The Journal of biological chemistry. 284(28):19142-19152.
Abstract
The Eleven Lysine-rich Leukemia (ELL) gene undergoes translocation and fuses in frame to the Mutiple Lineage Leukemia (MLL) gene in a substantial proportion of patients suffering from acute forms of leukemia. Studies show that ELL indirectly modulates transcription by serving as a regulator for transcriptional elongation as well as for p53, U19/Eaf2 and steroid receptor activities. Our in vitro and in vivo data demonstrate that ELL also could serve as a transcriptional factor to directly induce transcription of the thrombospondin-1 (TSP-1) gene. Experiments using ELL deletion mutants established that full length ELL is required for the TSP-1 up-regulation and that the transactivation domain likely resides in the C-terminal. Moreover, the DNA binding domain may localize to the first 45 amino acids of ELL. Not surprisingly, MLL-ELL, which lacks these amino acids, did not induce expression from the TSP-1 promoter. In addition, the ELL core response element appears to localize in the -1426 to -1418 region of TSP-1 promoter. Lastly, studies using zebrafish confirmed that ELL regulates TSP-1 mRNA expression in vivo and ELL could inhibit zebrafish vasculogenesis, at least in part, through up-regulating TSP-1. Given the importance of TSP-1 as an anti-angiogenic protein, our findings may have important ramifications for better understanding cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping