Meloni Alessandra, Incani Federica, Corda Denise, Cao Antonio, Rosatelli Maria Cristina
Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy.
Mol Immunol. 2008 Feb;45(3):805-9. doi: 10.1016/j.molimm.2007.06.156. Epub 2007 Aug 1.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomic autoimmune disease resulting from the defective function of a gene codifying for a transcription factor named autoimmune regulation (AIRE). The AIRE protein contains several domains among which two PHD fingers involved in the transcriptional activation. We investigated the function of the two PHD finger domains and the COOH terminal portion of AIRE by using several mutated constructs transfected in mammalian cells and a luciferase reporter assay. The results predict that the second PHD as well as the COOH terminal regions have marked transactivational properties. The COOH terminal region contains the fourth LXXLL and the PXXPXP motifs which play a critical role in mediating the transactivation capacity of the AIRE protein. Our study provides a definition of the role of the PHD fingers in transactivation and identifies a new transactivation domain of the AIRE protein localized in the COOH terminal region.
自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）是一种罕见的常染色体自身免疫性疾病，由一个编码名为自身免疫调节因子（AIRE）的转录因子的基因功能缺陷引起。AIRE蛋白包含几个结构域，其中两个PHD指结构域参与转录激活。我们通过使用转染到哺乳动物细胞中的几种突变构建体和荧光素酶报告基因检测，研究了AIRE的两个PHD指结构域和COOH末端部分的功能。结果预测，第二个PHD以及COOH末端区域具有显著的反式激活特性。COOH末端区域包含第四个LXXLL和PXXPXP基序，它们在介导AIRE蛋白的反式激活能力中起关键作用。我们的研究定义了PHD指结构域在反式激活中的作用，并确定了AIRE蛋白位于COOH末端区域的一个新的反式激活结构域。
