Self-association of CIITA and its transactivation potential.
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.
Sisk
T J
TJ
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Roys
S
S
Chang
C H
CH
D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005799:Genes, Dominant; D005802:Genes, MHC Class II; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D000596:Amino Acids; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D015847:Interleukin-4; D006160:Guanosine Triphosphate; D008156:Luciferases