ELL binding regulates U19/Eaf2 intracellular localization, stability, and transactivation.
BACKGROUND
U19/Eaf2, an androgen-response gene, is downregulated in advanced human prostate cancer specimens and its overexpression can markedly induce apoptosis in prostate cancer cells. Eleven-nineteen Lysine-rich Leukemia (ELL) is an RNA polymerase II transcription elongation factor, initially identified as a fusion partner gene of MLL in the t(11; 19) (q23; p13.1) chromosomal translocation in acute myeloid leukemia. U19/Eaf2 was previously reported as an ELL-associated factor, a potential transcription factor binds to ELL, forming nuclear speckles in vivo. These findings suggest that ELL-U19/Eaf2 interaction is potentially important in prostate cancer progression and/or acute myeloid leukemia. However, the functional significance of U19/Eaf2 interaction with ELL remains unclear.


METHODS
Using co-transfection, co-immunoprecipitation, protein stability assay and transactivation assay, we characterized the consequence of ELL binding to U19/Eaf2.


RESULTS
We provide further evidence for U19/Eaf2 as a transcription factor and show that ELL binding is required for nuclear speckle formation of human U19/Eaf2, stabilizes U19/Eaf2 and enhances its transactivation activity.


CONCLUSIONS
The above observations indicate ELL may be an important factor required for U19/Eaf2 function because U19/Eaf2 nuclear localization and transactivation activity are essential for its function as a transcription factor.
Xiao
Wuhan
W
Department of Urology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Jiang
Feng
F
Wang
Zhou
Z
D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D011471:Prostatic Neoplasms; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
C431383:EAF1 protein, human; C472771:EAF2 protein, human; D009838:Oligodeoxyribonucleotides; D014157:Transcription Factors; D008156:Luciferases