HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression.
During the prostate cancer (PCa) development and its progression into hormone independency, androgen receptor (AR) signals play a central role by triggering the regulation of target genes, including prostate-specific antigen. However, the regulation of these AR-mediated target genes is not fully understood. We have previously demonstrated a unique role of HOXB13 homeodomain protein as an AR repressor. Expression of HOXB13 was highly restricted to the prostate and its suppression dramatically increased hormone-activated AR transactivation, suggesting that prostate-specific HOXB13 was a highly potent transcriptional regulator. In this report, we demonstrated the action mechanism of HOXB13 as an AR repressor. HOXB13 suppressed androgen-stimulated AR activity by interacting with AR. HOXB13 did neither bind to AR responsive elements nor disturb nuclear translocation of AR in response to androgen. In PCa specimen, we also observed mutual expression pattern of HOXB13 and AR. These results suggest that HOXB13 not only serve as a DNA-bound transcription factor but play an important role as an AR-interacting repressor to modulate hormone-activated androgen receptor signals. Further extensive studies will uncover a novel mechanism for regulating AR-signaling pathway to lead to expose new role of HOXB13 as a non-DNA-binding transcriptional repressor.
Department of Anatomy, Chonnam National University Medical School, Gwangju, Korea.
Sin Do
SD
Kim
Ra-Young
RY
Park
Young-Rang
YR
Kim
In-Je
IJ
Kim
Taek Won
TW
Kang
Kwang Il
KI
Nam
Kyu Youn
KY
Ahn
Choon Sang
CS
Bae
Baik Youn
BY
Kim
Sung Sik
SS
Park
Chaeyong
C
Jung
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