Apoptosis Induction and Growth Suppression by U19/Eaf2 Is Mediated Through its ELL-Binding Domain

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. Prostate © 2006 Wiley-Liss, Inc.