The estrogen-responsive B box protein - A novel regulator of keratinocyte differentiation
The estrogen-responsive B box protein - A novel regulator of keratinocyte differentiation
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DOI：
10.1074/jbc.m111233200
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发表时间：
2002-06-07
影响因子：
4.8
通讯作者：
Werner, S
中科院分区：
文献类型：
--
作者：
Beer, HD;Munding, C;Werner, S
角质形成细胞生长因子（KGF）调节不同类型的上皮细胞（包括皮肤的角质形成细胞）的增殖、分化、迁移和存活。为了深入了解这些多重功能的机制，我们在角质形成细胞中寻找KGF调控的基因。利用差异显示反转录酶-PCR技术，我们确定了基因编码的雌激素反应B盒蛋白（EBBP），这是迄今尚未被功能上的特点。克隆全长鼠和人EBBP cDNA并完全测序。它们被证明编码75-kDa的蛋白质，主要定位于体外和体内角质形成细胞的细胞质中。在体内，EBBP被发现在高水平的KGF和表皮生长因子反应的基础角质形成细胞的人皮肤，但表达下调过度增厚的上皮细胞的皮肤伤口。EBBP在HaCaT角质形成细胞中的稳定过表达不影响转染细胞的增殖率，但增强了早期分化过程。这些结果表明，EBBP在基底角质形成细胞中的存在对于这些细胞的分化能力是重要的，并且需要下调过度增殖上皮中的EBBP表达以将细胞维持在非分化阶段。
Keratinocyte growth factor (KGF) regulates proliferation, differentiation, migration, and survival of different types of epithelial cells, including keratinocytes of the skin. To gain insight into the mechanisms underlying these multiple functions, we searched for KGF-regulated genes in keratinocytes. Using the differential display reverse transcriptase-PCR technology, we identified the gene encoding the estrogen-responsive B box protein (EBBP) which has as yet not been functionally characterized. The full-length murine and human EBBP cDNAs were cloned and fully sequenced. They were shown to encode 75-kDa proteins, which are mainly localized in the cytoplasm of keratinocytes in vitro and in vivo. In vivo, EBBP was found at high levels in the KGF and epidermal growth factor-responsive basal keratinocytes of human skin, but the expression was downregulated in the hyperthickened epithelium of skin wounds. Stable overexpression of EBBP in HaCaT keratinocytes did not affect the proliferation rate of the transfected cells, but enhanced the early differentiation process. These results suggest that the presence of EBBP in basal keratinocytes is important for the differentiation capacity of these cells, and that downregulation of EBBP expression in a hyperproliferative epithelium is required to maintain the cells in a non-differentiated stage.