Di Marco Barbara, Massetti Michela, Bruscoli Stefano, Macchiarulo Antonio, Di Virgilio Rosa, Velardi Enrico, Donato Valerio, Migliorati Graziella, Riccardi Carlo
Department of Clinical and Experimental Medicine IBiT Foundation, 06122 Perugia, Italy.
Nucleic Acids Res. 2007;35(2):517-28. doi: 10.1093/nar/gkl1080. Epub 2006 Dec 14.
Glucocorticoid-induced leucine zipper (GILZ) is a 137 amino acid protein, rapidly induced by treatment with glucocorticoids (GC), characterized by a leucine zipper (LZ) domain (76-97 amino acids), an N-terminal domain (1-75 amino acids) and a C-terminal PER domain (98-137 amino acids) rich in proline and glutamic acid residues. We have previously shown that GILZ binds to and inhibits NF-kappaB activity. In the present study we used a number of mutants with the aim of defining the GILZ molecular domains responsible for GILZ/p65NF-kappaB interaction. Results, obtained by in vitro and in vivo co-immunoprecipitation (Co-IP) and by transcriptional activity experiments, indicate that GILZ homo-dimerization, through the LZ domain, as well as the C-terminal PER domain, particularly the 121-123 amino acids, are both necessary for GILZ interaction with NF-kappaB, inhibition of transcriptional activity and of IL-2 synthesis.
糖皮质激素诱导亮氨酸拉链蛋白（GILZ）是一种由137个氨基酸组成的蛋白质，经糖皮质激素（GC）处理后可快速诱导产生，其特征在于具有一个亮氨酸拉链（LZ）结构域（76 - 97个氨基酸）、一个N端结构域（1 - 75个氨基酸）和一个富含脯氨酸和谷氨酸残基的C端PER结构域（98 - 137个氨基酸）。我们之前已经表明GILZ可结合并抑制核因子κB（NF-κB）的活性。在本研究中，我们使用了多种突变体，旨在确定负责GILZ/p65NF-κB相互作用的GILZ分子结构域。通过体外和体内共免疫沉淀（Co-IP）以及转录活性实验获得的结果表明，GILZ通过LZ结构域以及C端PER结构域（特别是121 - 123位氨基酸）进行同源二聚化，这对于GILZ与NF-κB相互作用、抑制转录活性以及白细胞介素-2合成均是必需的。
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