Glucocorticoid-induced leucine zipper (GILZ)/NF-kappaB interaction: role of GILZ homo-dimerization and C-terminal domain.
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.
Di Marco
Barbara
B
Department of Clinical and Experimental Medicine IBiT Foundation, 06122 Perugia, Italy.
Massetti
Michela
M
Bruscoli
Stefano
S
Macchiarulo
Antonio
A
Di Virgilio
Rosa
R
Velardi
Enrico
E
Donato
Valerio
V
Migliorati
Graziella
G
Riccardi
Carlo
C
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D016350:Leucine Zippers; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013601:T-Lymphocytes / Q000276:immunology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
C498608:Dsip1 protein, mouse; D007376:Interleukin-2; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014157:Transcription Factors