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Abstract
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.