Wuhan Xiao1, Feng Jiang, Zhou Wang. 1. Department of Urology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Abstract
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.
BACKGROUND:U19/Eaf2, an androgen-response gene, is downregulated in advanced humanprostate 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 humanU19/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.