E1AF, an ets-oncogene family transcription factor.
E1AF is an ets-oncogene family transcription factor. E1AF was shown to upregulate multiple matrix metalloproteinase (MMP) genes and contribute to the malignant phenotype of cancer cells by inducing invasive and metastatic activities. E1AF is upregulated by hepatocyte growth factor (HGF) stimulation, which indicates that E1AF would participate in cell motility by HGF/scatter factor. On the other hand, E1AF upregulates p21waf1/cip1 to induce cell cycle arrest when cells are exposed to stress. EWS/ETS fusions are frequently observed in Ewing's sarcoma, and we have revealed that EWS/ETS chimeric protein activates telomerase activity by upregulating hTERT. However, substitution ets binding site (EBS) mutants did not affect the responsiveness to EWS/E1AF. DNA-IP assay showed that the complexes contained EWS/E1AF bound to the hTERT promoter, which suggested that EWS/ETS functions as a co-activator for TERT transcription. Our findings that EWS/ETS acts as a transcriptional co-factor may imply that the transcription pathway is regulated by the interaction of transcription factors.
Shindoh
Masanobu
M
Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, N 13 W7, Kita-ku, Sapporo 060-8586, Japan. mshindoh@den.hokudai.ac.jp
Higashino
Fumihiro
F
Kohgo
Takao
T
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000494:pharmacology*; D002453:Cell Cycle; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000494:pharmacology*; D050783:Proto-Oncogene Proteins c-ets; D014158:Transcription, Genetic; D015854:Up-Regulation
D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020782:Matrix Metalloproteinases