Importance of acidic, proline/serine/threonine-rich, and GTP-binding regions in the major histocompatibility complex class II transactivator: generation of transdominant-negative mutants.
The class II transactivator (CIITA) is a master transcription regulator of gene products involved in the exogenous antigen presentation pathway, including major histocompatibility complex (MHC) class II, invariant chain, and DM. An extensive analysis of the putative functional domains of CIITA is undertaken here to explore the action of CIITA. Antibodies to CIITA protein were produced to verify that these mutant proteins are expressed. Both acidic and proline/serine/threonine-rich domains are essential for class II MHC promoter activation. In addition, three guanine nucleotide-binding motifs are essential for CIITA activity. Of these mutants, two exhibited strong transdominant-negative functions. These two mutants provide a plausible approach to manipulate MHC class II expression and immune responses.
Chin
K C
KC
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 27599-7295, USA.
Li
G G
GG
Ting
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005799:Genes, Dominant; D005802:Genes, MHC Class II; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D009842:Oligopeptides; D010455:Peptides; D011392:Proline; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D012694:Serine; D013912:Threonine; D015534:Trans-Activators / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D009842:Oligopeptides; D010455:Peptides; D015534:Trans-Activators; D013912:Threonine; D012694:Serine; C085706:FLAG peptide; D011392:Proline; D019204:GTP-Binding Proteins