GTP binding by class II transactivator: role in nuclear import

Class II transactivator (CIITA) is a global transcriptional coactivator of human leukocyte antigen–D (HLA-D) genes. CIITA contains motifs similar to guanosine triphosphate (GTP)–binding proteins. This report shows that CIITA binds GTP, and mutations in these motifs decrease its GTP-binding and transactivation activity. Substitution of these motifs with analogous sequences from Ras restores CIITA function. CIITA exhibits little GTPase activity, yet mutations in CIITA that confer GTPase activity reduce transcriptional activity. GTP binding by CIITA correlates with nuclear import. Thus, unlike other GTP-binding proteins, CIITA is involved in transcriptional activation that uses GTP binding to facilitate its own nuclear import.