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

Massimo Massetti, Barbara Di Marco, Stefano Bruscoli, Antonio Macchiarulo, Rosa Di Virgilio, Enrico Velardi, Valerio Donato, Graziella Migliorati, Carlo Riccardi

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)517-528
Number of pages12
JournalNucleic Acids Research
Volume35
DOIs
Publication statusPublished - 2007

Keywords

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Dimerization
  • Humans
  • Interleukin-2
  • Leucine Zippers
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B
  • Protein Structure, Tertiary
  • T-Lymphocytes
  • Transcription Factor RelA
  • Transcription Factors
  • Transcription, Genetic

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