EWS-Fli1 up-regulates expression of the Aurora A and Aurora B kinases.
Mol Cancer Res
; 6(12): 1937-45, 2008 Dec.
Article
in En
| MEDLINE
| ID: mdl-19074838
ABSTRACT
EWS-Fli1, a fusion gene resulting from the chromosomal translocation t(11;22, q24;q12), encodes a transcriptional activator, promotes cellular transformation, and is often found in Ewing sarcoma and primitive neuroectodermal tumor. The Aurora A and Aurora B kinases belong to a highly conserved family of serine/threonine protein kinases, are tightly regulated during the cell cycle, and are overexpressed in many carcinomas. Because the relationship between the Aurora A and/or Aurora B genes and the EWS-Fli1 fusion gene is unknown, we investigated the regulatory mechanism(s) by which Aurora kinases are controlled. Knockdown of EWS-Fli1 by small interfering RNA reduced mRNA levels not only of EWS-Fli1 but also of Aurora A and Aurora B. Luciferase assay using Aurora A and Aurora B promoters showed up-regulated activities compared with those of an empty vector. Experiments with deletion and point mutants showed positive regulatory Ets-binding sites located -84 and -71 bp upstream of the transcription initiation sites in Aurora A and Aurora B, respectively. Moreover, chromatin immunoprecipitation assay revealed that EWS-Fli1 gene products interact with both the Aurora A and Aurora B promoters. These results strongly suggest that the mitotic kinases Aurora A and Aurora B are regulated by EWS-Fli1 fusion protein in Ewing sarcoma cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoma, Ewing
/
Bone Neoplasms
/
Oncogene Proteins, Fusion
/
Protein Serine-Threonine Kinases
/
Proto-Oncogene Protein c-fli-1
Limits:
Humans
Language:
En
Journal:
Mol Cancer Res
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2008
Document type:
Article
Affiliation country: