Apoptosis Induction and Growth Suppression by U19/Eaf2 is Mediated Through Its ELL-binding Domain

Overview

Journal Prostate

Date 2006 Oct 18

PMID 17044034

Citations 12

Authors

Junghyun Hahn

Wuhan Xiao

Feng Jiang

Federico Simone

Michael J Thirman

Zhou Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

EAF2: a tumor suppressor gene with multi-aspect functions.

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Overview of research on fusion genes in prostate cancer.

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FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells.

Guo W, Keener A, Jing Y, Cai L, Ai J, Zhang J Prostate. 2015; 75(9):976-87.

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Identification of a genetic interaction between the tumor suppressor EAF2 and the retinoblastoma protein (Rb) signaling pathway in C. elegans and prostate cancer cells.

Cai L, Wang D, Fisher A, Wang Z Biochem Biophys Res Commun. 2014; 447(2):292-8.

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Pirin down-regulates the EAF2/U19 protein and alleviates its growth inhibition in prostate cancer cells.

Qiao Z, Wang D, Hahn J, Ai J, Wang Z Prostate. 2013; 74(2):113-20.

PMID: 24272884 PMC: 4827099. DOI: 10.1002/pros.22729.

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