Mutual trans activational repression of Runx2 and the androgen receptor by an impairment of their normal compartmentalization

被引:19
作者
Kawate, Hisaya
Wu, Yin
Ohnaka, Keizo
Takayanagi, Ryoichi
机构
[1] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan
[2] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Higashi Ku, Fukuoka 8128582, Japan
关键词
androgen receptor; Runx2; osteoblast; GFP; intranuclear foci; OSTEOCALCIN GENE-EXPRESSION; NUCLEAR HORMONE-RECEPTORS; GLUCOCORTICOID-RECEPTOR; INSENSITIVITY SYNDROME; TRANSCRIPTION FACTORS; LIVING CELLS; RUNX/CBFA/AML FACTORS; OSTEOBLASTIC CELLS; SUBNUCLEAR DOMAINS; TARGETING SIGNAL;
D O I
10.1016/j.jsbmb.2006.11.020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Steroid hormones play important roles not only in the reproductive system but also in bone metabolism. We examined the functional relationship between steroid hormone receptors and the Runx2 transcription factor that is essential for osteoblast differentiation and proliferation. A functional reporter assay using promoters carrying steroid hormone-responsive elements revealed that Runx2 suppressed ligand-dependent transcriptional activation mediated by receptors. To examine intracellular localization of these proteins, a three-dimensional imaging study was performed by laser scanning confocal microscopy of green fluorescent protein (GFP)-fused proteins. As previously reported, ligand-bound human androgen receptor (AR) was translocated from the cytoplasm to the nucleus and formed subnuclear fine foci. Coexpression of human Runx2 disrupted the AR subnuclear fine foci formation, and the intranuclear fluorescent pattern of AR became similar to that of Runx2. On the other hand, ligand-bound ARs repressed the Runx2-mediated transactivation function. Runx2 was also extracted from its original compartment by ligand-bound ARs. These results suggest that both Runx2 and ARs repress the transactivation function of the other protein by extracting it from its original compartment. The AR and Runx2 may play a mutual role in transcriptional activation in osteoblasts. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:46 / 56
页数:11
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