Mi Yang, Zhang Ye, Shen Yu-Fei
Department of Biochemistry and Molecular Biology, Chinese Academy of Medical Sciences, China.
Biochim Biophys Acta. 2011 Dec;1812(12):1675-80. doi: 10.1016/j.bbadis.2011.09.015. Epub 2011 Sep 29.
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.
含JmjC结构域的蛋白质无毛蛋白（HR）和维生素D受体（VDR）在维持头发生长中起关键作用。HR或VDR的突变会导致人类和小鼠脱发。在此我们表明，HR与VDR相互作用并诱导VDR在细胞核内重新定位。HR与定位于称为基质相关脱乙酰酶（MAD）小体的亚核结构的核受体共抑制因子（N-CoR）缔合并共定位。研究发现，与先天性全秃（AUC）或伴有丘疹性损害的无毛症（APL）相关的HR突变体（C622G、N970S、D1012N、V1136D），除了与VDR的共抑制活性受损外，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的共抑制活性。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。
