Elongation factor ELL (Eleven-Nineteen Lysine-rich Leukemia) acts as a transcription factor for direct thrombospondin-1 regulation.
The eleven-nineteen lysine-rich leukemia (ELL) gene undergoes translocation and fuses in-frame to the multiple lineage leukemia 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 could also 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 carboxyl terminus. Moreover, the DNA binding domain may localize to the first 45 amino acids of ELL. Not surprisingly, multiple lineage leukemia-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 the TSP-1 promoter. Finally, 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.
Zhou
Jiangang
J
Key Laboratory of Biodiversity and Conservation of Aquatic Organisms, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Feng
Xi
X
Ban
Bin
B
Liu
Jingxia
J
Wang
Zhou
Z
Xiao
Wuhan
W
D000818:Animals; D001483:Base Sequence; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017403:In Situ Hybridization; D007938:Leukemia / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D019700:Thrombospondin 1 / Q000096:biosynthesis*; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors / Q000378:metabolism* / Q000502:physiology*; D015027:Zebrafish
C090862:ELL protein, human; D019700:Thrombospondin 1; D035602:Transcriptional Elongation Factors