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.
Hahn
Junghyun
J
Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Xiao
Wuhan
W
Jiang
Feng
F
Simone
Federico
F
Thirman
Michael J
MJ
Wang
Zhou
Z
D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D008297:Male; D010449:Peptide Mapping; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D035602:Transcriptional Elongation Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
C472771:EAF2 protein, human; C090862:ELL protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors