Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer

Yueh Chiang Hu, Shuyuan Yeh, Shauh Der Yeh, Erik R. Sampson, Jiaoti Huang, Peng Li, Cheng Lung Hsu, Huei Ju Ting, Hui Kuan Lin, Liang Wang, Eungseok Kim, Jing Ni, Chawnshang Chang

Research output: Contribution to journalArticle

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Abstract

Androgen receptor (AR)-associated coregulator 70 (ARA70) was the first identified AR coregulator. However, its molecular mechanism and biological relevance to prostate cancer remain unclear. Here we show that ARA70 interacts with and promotes AR activity via the consensus FXXLF motif within the ARA70-N2 domain (amino acids 176-401). However, it does not promote AR activity via the classic LXXLL motif located at amino acids 92-96, although this classic LXXLL motif is important for ARA70 to interact with other receptors, such as PPARγ. The molecular mechanisms by which ARA70 enhances AR transactivation involve the increase of AR expression, protein stability, and nuclear translocation. Furthermore, ARA70 protein is more frequently detected in prostate cancer specimens (91.74%) than in benign tissues (64.64%, p <0.0001). ARA70 expression is also increased in high-grade prostate cancer tissues as well as the hormone-refractory LNCaP xenografts and prostate cancer cell lines. Because ARA70 can promote the antiandrogen hydroxyflutamide (HF)-enhanced AR transactivation, the increased ARA70 expression in hormone-refractory prostate tumors may confer the development of HF withdrawal syndrome, commonly diagnosed in patients with the later stages of prostate cancer. Because ARA70-N2 containing the AR-interacting FXXLF motif without coactivation function can suppress HF-enhanced AR transactivation in the hormone-refractory LNCaP cells, using the ARA70-N2 inhibitory peptide at the hormone refractory stage to battle the HF withdrawal syndrome may become an alternative strategy to treat prostate cancer.

Original languageEnglish
Pages (from-to)33438-33446
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number32
DOIs
Publication statusPublished - Aug 6 2004

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Androgen Receptors
Prostatic Neoplasms
Refractory materials
Hormones
Transcriptional Activation
Tissue
Amino Acids
Androgen Antagonists
Peroxisome Proliferator-Activated Receptors
Peptide Hormones
Protein Stability
Heterografts
Tumors
Prostate
Proteins
Cells
Cell Line
Peptides
hydroxyflutamide

ASJC Scopus subject areas

  • Biochemistry

Cite this

Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer. / Hu, Yueh Chiang; Yeh, Shuyuan; Yeh, Shauh Der; Sampson, Erik R.; Huang, Jiaoti; Li, Peng; Hsu, Cheng Lung; Ting, Huei Ju; Lin, Hui Kuan; Wang, Liang; Kim, Eungseok; Ni, Jing; Chang, Chawnshang.

In: Journal of Biological Chemistry, Vol. 279, No. 32, 06.08.2004, p. 33438-33446.

Research output: Contribution to journalArticle

Hu, YC, Yeh, S, Yeh, SD, Sampson, ER, Huang, J, Li, P, Hsu, CL, Ting, HJ, Lin, HK, Wang, L, Kim, E, Ni, J & Chang, C 2004, 'Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer', Journal of Biological Chemistry, vol. 279, no. 32, pp. 33438-33446. https://doi.org/10.1074/jbc.M401781200
Hu, Yueh Chiang ; Yeh, Shuyuan ; Yeh, Shauh Der ; Sampson, Erik R. ; Huang, Jiaoti ; Li, Peng ; Hsu, Cheng Lung ; Ting, Huei Ju ; Lin, Hui Kuan ; Wang, Liang ; Kim, Eungseok ; Ni, Jing ; Chang, Chawnshang. / Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 32. pp. 33438-33446.
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AU - Li, Peng

AU - Hsu, Cheng Lung

AU - Ting, Huei Ju

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AU - Kim, Eungseok

AU - Ni, Jing

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