Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D

The androgen receptor (AR) is a transcription factor that is pivotal for the development of prostate cancer. Here, we have identified two related histone demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We found that AR interacts through its ligand binding domain with JMJD...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-08, Vol.359 (3), p.742-746
Main Authors: Shin, Sook, Janknecht, Ralf
Format: Article
Language:English
Subjects:
Androgen receptor
Cell Line
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Histone demethylation
Histones - metabolism
Humans
JmjC domain
JMJD2
JMJD2A
JMJD2D
Jumonji Domain-Containing Histone Demethylases
Oxidoreductases - metabolism
Oxidoreductases, N-Demethylating - genetics
Oxidoreductases, N-Demethylating - metabolism
Prostate cancer
Prostate-specific antigen
Protein Binding
Receptors, Androgen - genetics
Receptors, Androgen - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic - genetics
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Summary:The androgen receptor (AR) is a transcription factor that is pivotal for the development of prostate cancer. Here, we have identified two related histone demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We found that AR interacts through its ligand binding domain with JMJD2A and JMJD2D. On the other hand, JMJD2A utilizes its catalytic domain or C-terminus to bind to AR, and JMJD2D does so via its C-terminus. Further, overexpression of JMJD2A or D stimulates AR function and this is dependent on JMJD2 catalytic activity. Conversely, downregulation of JMJD2A, which is often overexpressed in prostate tumors, reduces basal transcription of the AR target gene, prostate-specific antigen, in LNCaP prostate cancer cells. Altogether, our data have identified a novel class of AR coactivators, whose (over)expression in prostate tumors could contribute to the constitutive activation of AR and thus to androgen-depletion independency of advanced prostate cancer cells.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.05.179