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

• Published in: Nucleic acids research Vol. 35; no. 2; pp. 517 - 528
• Main Authors: Marco, Barbara Di, Massetti, Michela, Bruscoli, Stefano, Macchiarulo, Antonio, Virgilio, Rosa Di, Velardi, Enrico, Donato, Valerio, Migliorati, Graziella, Riccardi, Carlo
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.01.2007
• Subjects: Molecular Biology
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkl1080

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-κB activity. In the present study we used a number of mutants with the aim of defining the GILZ molecular domains responsible for GILZ/p65NF-κB 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-κB, inhibition of transcriptional activity and of IL-2 synthesis.