Deleted in Breast Cancer 1, a Novel Androgen Receptor (AR) Coactivator That Promotes AR DNA-binding Activity
Deleted in Breast Cancer 1, a Novel Androgen Receptor (AR) Coactivator That Promotes AR DNA-binding Activity
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乳腺癌 1 中删除了一种新型雄激素受体 (AR) 共激活剂，可促进 AR DNA 结合活性
DOI：
10.1074/jbc.m808988200
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发表时间：
2009-03-13
影响因子：
4.8
通讯作者：
Wong, Jiemin
中科院分区：
文献类型：
--
作者：
Fu, Junjiang;Jiang, Jun;Wong, Jiemin
雄激素受体（AR）在男性生殖功能的发育和维持以及前列腺癌的发病中起着关键作用。作为一种配体调控的转录因子，AR辅调节子的鉴定和表征对于理解其多种生物学功能的分子机制至关重要。在这里，我们报告了一种新的AR辅激活因子的鉴定，在乳腺癌1（DBC1）中删除，通过生化方法。DBC1以配体刺激的方式与AR相互作用，并促进转染细胞以及非洲爪蟾卵母细胞中的AR转录激活。在体外凝胶迁移实验中，重组DBC 1大大增强AR DNA结合活性。在前列腺癌细胞系LNCaP中，DBC1的表达也增强了AR与染色质化模板的结合，而DBC1的敲低损害了AR与内源性前列腺特异性抗原（PSA）基因的结合。因此，我们的数据确定DBC1作为一种新的AR共激活剂。
Androgen receptor (AR) plays a critical role in development and maintenance of male reproductive functions and the etiology of prostate cancer. As a ligand-regulated transcription factor, identification and characterization of AR coregulators are essential for understanding the molecular mechanisms underlying its diverse biological functions. Here we reported the identification of a novel AR coactivator, deleted in breast cancer 1 (DBC1), through a biochemical approach. DBC1 interacts with AR in a ligand-stimulated manner and facilitates AR transcriptional activation in transfected cells as well as in Xenopus oocytes. In in vitro gel shift experiments, recombinant DBC1 drastically enhanced AR DNA-binding activity. Expression of DBC1 also enhanced the binding of AR to chromatinized template in vivo, whereas knockdown of DBC1 impaired the binding of AR to endogenous prostate-specific antigen (PSA) gene in the prostate cancer cell line LNCaP. Thus, our data identify DBC1 as a novel AR coactivator.