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, B., Massetti, M., Bruscoli, S., Macchiarulo, A., Di Virgilio, R., Velardi, E., Donato, V., Migliorati, G., Riccardi, C., Glucocorticoid-induced leucine zipper (GILZ)/NF-kappaB interaction: role of GILZ homo-dimerization and C-terminal domain, <<NUCLEIC ACIDS RESEARCH>>, 2007; 35 (2): 517-528. [doi:10.1093/nar/gkl1080] [http://hdl.handle.net/10807/103964]
Glucocorticoid-induced leucine zipper (GILZ)/NF-kappaB interaction: role of GILZ homo-dimerization and C-terminal domain
Massetti, Massimo;
2007
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.