ARA24/Ran enhances the androgen-dependent NH2- and COOH-terminal interaction of the androgen receptor.
The androgen receptor (AR) acts as an androgen-dependent transcription factor controlling the development of prostate tissue. Upon binding to androgen, AR undergoes a dynamic structural change leading to interaction between the NH(2)- and COOH-terminal regions of AR (N-C interaction). ARA24/Ran, which is a small GTPase, functions as an AR coactivator. Here, we report that ARA24/Ran enhances the N-C interaction of AR. The constitutively GTP- or GDP-bound form of ARA24/Ran repressed the AR N-C interaction. ARA24/Ran did not enhance the transcriptional activities of AR mutants that disrupt the N-C interaction. ARA24/Ran formed an endogenous protein complex with nuclear AR, but not cytoplasmic AR. Unlike SRC-1 with the positive activity for AR N-C interaction, ARA24/Ran did not enhance the transcriptional activity of the COOH-terminal domain-deleted AR mutant that is constitutively localized in the nucleus. These data demonstrate that ARA24/Ran increases AR transactivation by enhancing the AR N-C interaction in the nucleus.
Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan.
Naoki
N
Harada
Yuji
Y
Ohmori
Ryoichi
R
Yamaji
Yasuki
Y
Higashimura
Kazuki
K
Okamoto
Fumihide
F
Isohashi
Yoshihisa
Y
Nakano
Hiroshi
H
Inui
D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000728:Androgens; C120587:RAN protein, human; D011944:Receptors, Androgen; D020931:ran GTP-Binding Protein