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Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL‐binding domain
Author(s) -
Hahn Junghyun,
Xiao Wuhan,
Jiang Feng,
Simone Federico,
Thirman Michael J.,
Wang Zhou
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20481
Subject(s) - apoptosis , downregulation and upregulation , myeloid leukemia , biology , cell growth , cancer research , programmed cell death , prostate cancer , transfection , microbiology and biotechnology , hek 293 cells , receptor , cancer , cell culture , gene , biochemistry , genetics
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.