Glucocorticoid-induced leucine zipper (GILZ)/NF-kappaB interaction: role of GILZ homo-dimerization and C-terminal domain

• Published in: Nucleic acids research Vol. 35; no. 2; pp. 517 - 528
• Main Authors: Di Marco, Barbara, Massetti, Michela, Bruscoli, Stefano, Macchiarulo, Antonio, Di Virgilio, Rosa, Velardi, Enrico, Donato, Valerio, Migliorati, Graziella, Riccardi, Carlo
• Format: Journal Article
• Language: English
• Published: England 2007
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Cell Line; Dimerization; Humans; Interleukin-2 - biosynthesis; Leucine Zippers; Mice; Models, Molecular; Molecular Sequence Data; Mutation; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Protein Structure, Tertiary; T-Lymphocytes - immunology; Transcription Factor RelA - antagonists & inhibitors; Transcription Factor RelA - metabolism; Transcription Factors - chemistry; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 1362-4962

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.