Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain |
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Authors: | Hahn Junghyun Xiao Wuhan Jiang Feng Simone Federico Thirman Michael J Wang Zhou |
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Affiliation: | Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. |
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Abstract: | BACKGROUND: U19/Eaf2 is an androgen-response gene and its downregulation is frequently observed in advanced human prostate cancer. U19/Eaf2 interacts with ELL, a fusion partner of MLL in the (11;19) (q23;p13.1) translocation in acute myeloid leukemia. U19/Eaf2 overexpression induces apoptosis and suppresses xenograft tumor growth. METHODS: Transfection and colony formation were used to assay for apoptosis and growth suppression of various U19/Eaf2 mutants. Co-immunoprecipitation was performed to test the interaction between the U19/Eaf2 constructs and ELL. RESULTS: The region of U19/Eaf2 essential for apoptosis and growth suppression was mapped to amino acids 68-113. This region was necessary and sufficient for binding ELL. Co-expression of U19/Eaf2 and ELL in 293 cells lead to significant increase in cell death and growth suppression. CONCLUSIONS: These observations argue that the interaction with ELL is essential for the induction of apoptosis and growth suppression by U19/Eaf2. |
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Keywords: | U19/Eaf2 ELL apoptosis growth suppression prostate cancer |
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