Dendritic cell-specific MHC class II transactivator contains a caspase recruitment domain that confers potent transactivation activity.
The MHC class II transactivator (CIITA) is a critical transcription factor that regulates genes involved in antigen presentation function. At least three functional forms of CIITA gene products are transcribed from three different promoters. The CIITA gene expressed in dendritic cells (DC-CIITA) has a unique first exon encoding an extended N-terminal region of CIITA. Here, we show that the N terminus of DC-CIITA has high homology to a caspase recruitment domain (CARD) found in components of apoptosis and nuclear factor-kappaB signaling pathways. However, DC-CIITA does not regulate cell death, nor does it induce nuclear factor-kappaB activity. Instead, DC-CIITA is transcriptionally a more potent activator of the MHC class II gene than the form expressed in B cells. A single amino acid substitution in the CARD of DC-CIITA, predicted to disrupt CARD-CARD interactions, diminished the transactivation potential of DC-CIITA. These results indicate that the CARD in the context of CIITA serves as a regulatory domain for transcriptional activity and may function to selectively enhance MHC class II gene expression in dendritic cells.
Nickerson
K
K
Department of Microbiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Sisk
T J
TJ
Inohara
N
N
Yee
C S
CS
Kennell
J
J
Cho
M C
MC
Yannie
P J
PJ
Nunez
G
G
Chang
C H
CH
D000595:Amino Acid Sequence; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000737:chemistry*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005434:Flow Cytometry; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
C083728:MHC class II transactivator protein; D016328:NF-kappa B; D009687:Nuclear Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D004247:DNA; D008156:Luciferases; D020169:Caspases