DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts
DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts
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DOI：
10.1016/j.bbadis.2010.06.001
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发表时间：
2010-09-01
影响因子：
6.2
通讯作者：
Sakurai, Hiroshi
中科院分区：
文献类型：
--
作者：
Enoki, Yasuaki;Mukoda, Yuka;Sakurai, Hiroshi
热休克转录因子HSF4是晶状体发育和纤维细胞分化所必需的。人类HSF4基因的突变与先天性和年龄相关性白内障有关。在这里，我们发现HSF4激活晶状体上皮细胞中编码晶体蛋白和珠状丝结构蛋白的基因转录。五种与先天性白内障相关的错义突变抑制了HSF4的dna结合，这表明HSF4突变、晶状体蛋白基因表达缺失与白内障发生之间存在关联。然而，两种与年龄相关性白内障相关的错义突变没有或仅轻微改变HSF4的活性，这意味着其他遗传和环境因素影响了这些突变蛋白的功能。(C) 2010 Elsevier B.V.版权所有
Heat shock transcription factor HSF4 is necessary for ocular lens development and fiber cell differentiation. Mutations of the human HSF4 gene have been implicated in congenital and age-related cataracts. Here, we show that HSF4 activates transcription of genes encoding crystallins and beaded filament structural proteins in lens epithelial cells. Five missense mutations that have been associated with congenital cataract inhibited DNA-binding of HSF4, which demonstrates the relationship between HSF4 mutations, loss of lens protein gene expression, and cataractogenesis. However, two missense mutations that have been associated with age-related cataract did not or only slightly alter HSF4 activity, implying that other genetic and environmental factors affect the functions of these mutant proteins. (C) 2010 Elsevier B.V. All rights reserved.