論文

基本情報

氏名 河手 久弥
氏名(カナ) カワテ ヒサヤ
氏名(英語) HISAYA KAWATE
所属 中村学園大学 栄養科学部 栄養科学科
職名 教授

題名

Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients

単著・共著の別

共著

著者

Hisaya Kawate
Yin Wu
Keizo Ohnaka
Rong-Hua Tao
Kei-Ichiro Nakamura
Taijiro Okabe
Toshihiko Yanase
Hajime Nawata
Ryoichi Takayanagi

担当区分

概要

Context: Recent imaging studies revealed that androgen receptor (AR) is ligand-dependently translocated from the cytoplasm into the nucleus and forms intranuclear fine foci. In this study, we examined whether intracellular dynamics of mutant ARs detected in two androgen insensitivity syndrome (AIS) patients was impaired.
Objective: ARs with mutations in the DNA-binding domain were functionally characterized and compared with the wild-type AR.
Patients: In a complete AIS patient ( subject 1), cysteine residue 579 in the first zinc finger motif of AR was substituted for phenylalanine (AR-C579F). Another mutation (AR-F582Y) was found in a partial AIS patient (subject 2).
Results: AR-F582Y retained less than 10% of the transactivation activity of the wild-type AR, whereas no ligand-dependent transactivation was detected for AR-C579F. Image analyses of the receptors fused to green fluorescent protein showed that the wild-type AR was ligand-dependently translocated into the nucleus in which it formed fine subnuclear foci. Surprisingly, after the addition of dihydrotestosterone, the two mutant ARs initially formed large cytoplasmic dots, many of which were found to be close to mitochondria by electron microscopy. Subsequently, a part of the ligand-bound mutant ARs gradually entered the nucleus to form a smaller number of larger dots, compared with the wild-type AR. Fluorescence recovery after photobleaching analysis revealed that the intranuclear mobility of the mutant ARs decreased, compared with that of the wild-type AR.
Conclusions: These results suggest that the abnormal translocation, localization, and mobility of the mutant ARs may be the cause of AIS in these subjects.

発表雑誌等の名称

Journal of Clinical Endocrinology and Metabolism

出版者

ENDOCRINE SOC

90

11

開始ページ

6162

終了ページ

6169

発行又は発表の年月

2005/11

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

国際共著

ISSN

0021-972X

eISSN

DOI

10.1210/jc.2005-0179

Cinii Articles ID

Cinii Books ID

Pubmed ID

16118342

PubMed Central 記事ID

形式

無償ダウンロード

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID