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.
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
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping