Self-Association of CIITA and Its Transactivation Potential

Abstract

The major histocompatibility complex (MHC) class II transactivator (CIITA) regulates the expression of genes involved in the immune response, including MHC class II genes and the interleukin-4 gene. Interactions between CIITA and sequence-specific, DNA-binding proteins are required for CIITA to function as an activator of MHC class II genes. CIITA also interacts with the coactivators CBP (also called p300), and this interaction leads to synergistic activation of MHC class II promoters. Here, we report that CIITA forms complexes with itself and that a central region, including the GTP-binding domain is sufficient for self-association. Additionally, this central region interacts with the C-terminal leucine-rich repeat as well as the N-terminal acidic domain. LXXLL motifs residing in the GTP-binding domain are essential for self-association. Finally, distinct differences exist among various CIITA mutant proteins with regard to activation function, subcellular localization, and association with wild-type protein and dominant-negative potential.

ACKNOWLEDGMENTS

We thank Naohiro Inohara and Gabriel Nunez for stimulating discussions of published and unpublished data and Jenny Ting for CIITA expression plasmids. We also express our immense appreciation to Wes Dunnick and Ormond MacDougald and to Tania Gourley for critical review of the manuscript.

This work was supported in part by National Institutes of Health grant AI41510 to C.-H. Chang and Immunology Training Grant T32-AI07413 to T. J. Sisk.