Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis

Cheng Lung Hsu; Jai Shin Liu; Po Long Wu; Hong Hsiang Guan; Yuh Ling Chen; An Chi Lin; Huei Ju Ting; See Tong Pang; Shauh Der Yeh; Wen Lung Ma; Chung Jung Chen; Wen Guey Wu; Chawnshang Chang

doi:10.1016/j.molonc.2014.06.009

Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis

Cheng Lung Hsu
, Jai Shin Liu
, Po Long Wu
, Hong Hsiang Guan
, Yuh Ling Chen
, An Chi Lin
, Huei Ju Ting
, See Tong Pang
, Shauh Der Yeh
, Wen Lung Ma
, Chung Jung Chen
, Wen Guey Wu
, Chawnshang Chang^*

^*Corresponding author for this work

School of Medicine

Chang Gung University
National Tsing Hua University
National Synchrotron Radiation Center
University of Rochester
National Cheng Kung University
China Medical University Taichung

Research output: Contribution to journal › Journal Article › peer-review

56 Scopus citations

Abstract

Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.

Original language	English
Pages (from-to)	1575-1587
Number of pages	13
Journal	Molecular Oncology
Volume	8
Issue number	8
DOIs	https://doi.org/10.1016/j.molonc.2014.06.009
State	Published - 01 12 2014

Bibliographical note

Publisher Copyright:
© 2014 Federation of European Biochemical Societies.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Androgen receptor
Anti-androgen withdrawal syndrome
BUD31
Crystallography
FxxLF

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10.1016/j.molonc.2014.06.009

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Hsu, C. L., Liu, J. S., Wu, P. L., Guan, H. H., Chen, Y. L., Lin, A. C., Ting, H. J., Pang, S. T., Yeh, S. D., Ma, W. L., Chen, C. J., Wu, W. G., & Chang, C. (2014). Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis. Molecular Oncology, 8(8), 1575-1587. https://doi.org/10.1016/j.molonc.2014.06.009

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title = "Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis",

abstract = "Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.",

keywords = "Androgen receptor, Anti-androgen withdrawal syndrome, BUD31, Crystallography, FxxLF",

author = "Hsu, \{Cheng Lung\} and Liu, \{Jai Shin\} and Wu, \{Po Long\} and Guan, \{Hong Hsiang\} and Chen, \{Yuh Ling\} and Lin, \{An Chi\} and Ting, \{Huei Ju\} and Pang, \{See Tong\} and Yeh, \{Shauh Der\} and Ma, \{Wen Lung\} and Chen, \{Chung Jung\} and Wu, \{Wen Guey\} and Chawnshang Chang",

note = "Publisher Copyright: {\textcopyright} 2014 Federation of European Biochemical Societies.",

year = "2014",

month = dec,

day = "1",

doi = "10.1016/j.molonc.2014.06.009",

language = "英语",

volume = "8",

pages = "1575--1587",

journal = "Molecular Oncology",

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Hsu, CL, Liu, JS, Wu, PL, Guan, HH, Chen, YL, Lin, AC, Ting, HJ, Pang, ST, Yeh, SD, Ma, WL, Chen, CJ, Wu, WG & Chang, C 2014, 'Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis', Molecular Oncology, vol. 8, no. 8, pp. 1575-1587. https://doi.org/10.1016/j.molonc.2014.06.009

Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis. / Hsu, Cheng Lung; Liu, Jai Shin; Wu, Po Long et al.
In: Molecular Oncology, Vol. 8, No. 8, 01.12.2014, p. 1575-1587.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis

AU - Hsu, Cheng Lung

AU - Liu, Jai Shin

AU - Wu, Po Long

AU - Guan, Hong Hsiang

AU - Chen, Yuh Ling

AU - Lin, An Chi

AU - Ting, Huei Ju

AU - Pang, See Tong

AU - Yeh, Shauh Der

AU - Ma, Wen Lung

AU - Chen, Chung Jung

AU - Wu, Wen Guey

AU - Chang, Chawnshang

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.

AB - Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.

KW - Androgen receptor

KW - Anti-androgen withdrawal syndrome

KW - BUD31

KW - Crystallography

KW - FxxLF

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U2 - 10.1016/j.molonc.2014.06.009

DO - 10.1016/j.molonc.2014.06.009

M3 - 文章

C2 - 25091737

AN - SCOPUS:84911968222

SN - 1574-7891

VL - 8

SP - 1575

EP - 1587

JO - Molecular Oncology

JF - Molecular Oncology

IS - 8

ER -

Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis

Abstract

Bibliographical note

UN SDGs

Keywords

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