Mechanism of JmjC-containing protein Hairless in the regulation of vitamin D receptor function
Mechanism of JmjC-containing protein Hairless in the regulation of vitamin D receptor function
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JmjC蛋白Hairless调节维生素D受体功能的机制
DOI：
10.1016/j.bbadis.2011.09.015
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发表时间：
2011-12-01
影响因子：
6.2
通讯作者：
Shen, Yu-fei
中科院分区：
文献类型：
--
作者：
Mi, Yang;Zhang, Ye;Shen, Yu-fei
含有 JmjC 结构域的蛋白质 Hairless (HR) 和维生素 D 受体 (VDR) 在维持头发生长中发挥着关键作用。 HR 或 VDR 突变会导致人类和小鼠脱发。在这里，我们表明 HR 与 VDR 相互作用并诱导 VDR 在细胞核中重新定位。 HR 与核受体辅阻遏物 (N-CoR) 关联并共定位，核受体辅阻遏物 (N-CoR) 定位于称为基质相关脱乙酰酶 (MAD) 体的亚核结构。研究发现，与先天性普秃 (AUC) 或伴有丘疹性病变的无毛症 (APL) 相关的 HR 突变体（C622G、N970S、D1012N、V1136D）除了 VDR 共抑制活性受损外，还表现出异常的亚细胞分布。对 HR 缺失突变体的研究表明，JmjC 结构域有助于 HR 的共阻遏活性。我们的工作为理解HR在头发生长中的作用提供了新的线索和证据。 (C) 2011 Elsevier B.V. 保留所有权利。
The JmjC-domain-containing protein Hairless (HR) and the vitamin D receptor (VDR) play a critical role in the maintenance of hair growth. Mutations in HR or VDR cause alopecia in humans and mice. Here we show that HR interacts with VDR and induces VDR relocalization in the nuclei. HR associates and colocalizes with nuclear receptor co-repressor (N-CoR) which is localized to subnuclear structures termed matrix-associated deacetylase (MAD) bodies. It is found that the HR mutants (C622G, N970S, D1012N, V1136D), associated with alopecia universalis congenita (AUC) or atrichia with papular lesions (APL), exhibit an abnormal subcellular distribution in addition to the impaired co-repressor activity with VDR. Studies on deletion mutants of HR indicate that the JmjC domain contributes to the co-repressor activity of HR. Our work provides new clues and evidence for the understanding on the role of HR in hair growth. (C) 2011 Elsevier B.V. All rights reserved.