Glucocorticoid-induced leucine zipper (GILZ) is a leucine zipper protein ex-pressed in normal lymphocytes from thymus, spleen and lymph nodes. It is absent in nonlymphoid tissues including brain, liver and kidney. GILZ mediates the immunosuppressive effects of glucocorticoid hormones; its expression is induced in T cells by dexamethasone. GILZ protects T cells from an anti-CD3 antibody-induced apoptosis by inhibiting Fas and Fas ligand expression. It interferes with Egr-2, Egr-3, NFAT/AP-1-inducible transcription factors and AP-1. The interaction of GILZ with c-Fos and c-Jun inhibits the binding of active AP-1 to its DNA consensus site in vitro. GILZ also binds NFkB subunits and inhibits the NFkB nuclear translocation. It inhibits T cell receptor-induced interleukin-2/interleukin-2 receptor expression. The binding of GILZ to Raf-1 prevents Raf-MEK-ERK activation in the MAPK pathway. GILZ is expressed by normal macrophages in nonlymphoid tissues and by tumor-infiltrating macrophages in Burkitt lymphomas. The gene encoding human GILZ maps to chromosome Xq22.3.
