Identification of a conserved cluster of skin-specific genes encoding secreted proteins

Identification of a conserved cluster of skin-specific genes encoding secreted proteins
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DOI:
10.1016/j.gene.2004.03.010
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发表时间:
2004-06-09
期刊:
影响因子:
3.5
通讯作者:
Lanctôt, C
Lanctôt, C
中科院分区:
生物学3区
文献类型:
--
作者:
Moffatt, P;Salois, P;Lanctôt, C

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角质形成细胞的终末分化导致由交联的细胞内和细胞外物质组成的角质层的形成。使用信号陷阱表达筛选策略,我们已经确定了四个cDNA编码分泌蛋白可能参与这一过程。其中一个cDNA与最近描述的表皮特异性蛋白suprapasin的短同种型相同,该蛋白在此显示含有功能性分泌信号。第二个cDNA,sk 89,编码493个氨基酸的蛋白质,富含甘氨酸和丝氨酸残基。第三个cDNA编码SK 89的C-末端片段(氨基酸410-493)。它包含SK 89基因座的外显子13至18,但转录起始于编码不同分泌信号的同种型特异性外显子。第四个cDNA编码角质形成细胞分化相关蛋白(KDAP),一种102个氨基酸的前体蛋白。免疫荧光亚细胞定位和Western印迹标记蛋白的检测证实,这四种蛋白质的分泌。北方分析和原位杂交显示,相应基因的表达仅限于表皮的基底上角质形成细胞。这些编码表皮特异性分泌产物的基因存在于人染色体19q13.12和小鼠染色体7A 3上的保守簇中。(C)2004 Elsevier B. V.保留所有权利。
Terminal differentiation of keratinocytes results in the formation of a cornified layer composed of cross-linked intracellular and extracellular material. Using a signal trap expression screening strategy, we have identified four cDNAs encoding secreted proteins potentially involved in this process. One of the cDNAs is identical to the short isoform of suprabasin, a recently described epidermis-specific protein, which is shown here to contain a functional secretory signal. The second cDNA, sk89, encodes a protein of 493 amino acids, rich in glycine and serine residues. The third cDNA encodes a C-terminal fragment of SK89 (amino acids 410-493). It comprises exons 13 to 18 of the sk89 locus but transcription starts at an isoform-specific exon encoding a distinct secretory signal. The fourth cDNA encodes keratinocyte differentiation-associated protein (KDAP), a precursor protein of 102 amino acids. Subcellular localization by immunofluorescence and detection of the tagged proteins by Western blotting confirmed that the four proteins are secreted. Northern analysis and in situ hybridization revealed that expression of the corresponding genes was restricted to the suprabasal keratinocytes of the epidermis. These genes encoding epidermis-specific secreted products are found in a conserved cluster on human chromosome 19q13.12 and on mouse chromosome 7A3. (C) 2004 Elsevier B.V. All rights reserved.