Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a novel mammalian Grainyhead-like factor
Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a novel mammalian Grainyhead-like factor
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DOI：
10.1002/dvdy.10255
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发表时间：
2003-04-01
影响因子：
2.5
通讯作者：
Andersen, B
中科院分区：
文献类型：
--
作者：
Kudryavtseva, EI;Sugihara, TM;Andersen, B
LMO-4是一种仅限lim的因子，在许多上皮细胞中高表达，包括表皮细胞和毛囊细胞。由于LMOs可能通过与dna结合蛋白相互作用而发挥作用，我们使用酵母双杂交系统筛选小鼠皮肤文库中lmo -4相互作用的dna结合蛋白。在这个筛选中，我们分离了一个新的lmo -4相互作用因子，与果蝇基因Grainyhead高度相关。粒头在蝇胚表皮上表达，在表皮形成中起重要作用。随着这一新的哺乳动物Grainyhead-like epithelial transactivator 1 （GET-1）基因的鉴定，已知的哺乳动物Grainyhead-like基因家族成员扩展到6个，根据序列同源性分为两类。有趣的是，GET-1的表达模式与果蝇相似，在体外胚层/表皮中表达最高，但在胃肠道、泌尿生殖系统和呼吸道的上皮细胞中也有表达。GET-1蛋白定位于细胞核并结合至少一个粒头dna结合位点。GET-1 dna结合域映射到一个与果蝇Grainyhead dna结合域同源的区域。GET-1在溶液中通过一个短的c端结构域进行二聚，该结构域与其他类似grainyhead的基因同源。位于氨基酸100和190之间的短结构域与已知的反激活结构域没有同源性，足以使异源GAL4 dna结合结构域被反激活。此外，GET-1似乎包含抑制结构域，这与Grainyhead和其他哺乳动物Grainyhead样基因可以同时作为激活因子和抑制因子的观察结果一致。这些数据表明GET-1是一种转录调节因子，可能在哺乳动物上皮组织中发挥重要作用。(C) 2003 Wiley-Liss, Inc。
LMO-4 is an LIM-only factor that is highly expressed in many epithelial cells, including those of the epidermis and hair follicles. Because LMOs may function by interacting with DNA-binding proteins, we have used the yeast two-hybrid system to screen mouse skin libraries for LMO-4-interacting DNA-binding proteins. In this screen, we isolated a novel LMO-4-interacting factor highly related to the Drosophila gene Grainyhead. Grainyhead is epidermally expressed and carries out important functions in cuticular formation in the fly embryo. With the identification of this novel mammalian Grainyhead-like gene, referred to as Grainyhead-like epithelial transactivator 1 (GET-1), the known members of the mammalian Grainyhead-like gene family are extended to six, failing into two classes based on sequence homology. Of interest, the expression pattern of GET-1 is similar to that of Drosophila Grainyhead with highest expression in the somatic ectoderm/epidermis, but GET-1 is additionally expressed in epithelial cells of gastrointestinal, genitourinary, and respiratory tracks. The GET-1 protein localizes to the nucleus and binds to at least one Grainyhead DNA-binding site. The GET-1 DNA-binding domain maps to a region containing homology to the Drosophila Grainyhead DNA-binding domain. GET-1 homodimerizes in solution by means of a short C-terminally located domain that is homologous to other Grainyhead-like genes. A short domain located between amino acids 100 and 190, which bears no homology to known transactivation domains, is sufficient to confer transactivation to the heterologous GAL4 DNA-binding domain. In addition, GET-1 appears to contain repression domains consistent with the observation that Grainyhead and other mammalian Grainyhead-like genes can act both as activators and repressors. These data suggest that GET-1 is a transcriptional regulator that may perform important functions in epithelial tissues of mammals. (C) 2003 Wiley-Liss, Inc.