Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2
Functional analysis of MITF gene mutations associated with Waardenburg syndrome type 2
复制标题
2 型瓦登堡综合征相关 MITF 基因突变的功能分析
DOI：
10.1016/j.febslet.2012.10.006
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发表时间：
2012-11-30
期刊：
影响因子：
3.5
通讯作者：
Feng, Yong
中科院分区：
文献类型：
--
作者：
Zhang, Hua;Luo, Hunjin;Feng, Yong
小眼畸形相关转录因子（MITF）突变会导致黑素细胞发育异常，并引发2型瓦登伯格综合征（WS2）。在此，我们分析了最近发现的两种与WS2相关的MITF突变（p.R217I和p.T192fsX18）的体外活性。R217I突变型MITF保留了部分活性、正常的DNA结合能力及核内分布，而T192fsX18突变型MITF无法激活酪氨酸酶（TYR）启动子，且显示出异常的亚细胞定位，这可能是由于213 - 218位氨基酸（ERRRRF）处的核定位信号（NLS）缺失所致。这些结果表明，单倍体不足可能是这两种突变导致WS2轻度表型的潜在机制。（C）2012欧洲生物化学学会联合会。由爱思唯尔B.V.出版。保留所有权利。
MITF mutations results in an abnormal melanocyte development and lead to Waardenburg syndrome type 2 (WS2). Here, we analyzed the in vitro activities of two recently identified WS2-associated MITF mutations (p.R217I and p.T192fsX18). The R217I MITF retained partial activity, normal DNA-binding ability and nuclear distribution, whereas the T192fsX18 MITF failed to activate TYR promoter and showed aberrant subcellular localization which may be caused by deletion of nuclear localization signal (NLS) at aa 213-218 (ERRRRF). These results suggest that haploinsufficiency may be the underlying mechanism for the mild phenotypes of WS2 caused by these two mutations. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.