Isoforms of the class II transactivator protein.
The class II transactivator (CIITA) controls both the constitutive and IFN-gamma inducible expression of HLA-D genes. In addition, through the squelching of another transactivator CREB-binding protein, CIITA was more recently shown to have a wider cellular function, including cell cycle control or cellular response to IFN-gamma and IL-4. However, due to its low expression level, its analysis mainly relies on the study of recombinant overexpressed forms of the protein. We report here the analysis of native CIITA in various cell types. We first show the precise timing of CIITA protein expression in a fibroblast cell line in response to IFN-gamma. This expression is observed 2 h after the cytokine addition with a peak of expression ranging from 16 to 24 h. We next show the existence of two major isoforms of the CIITA protein differentially expressed in fibroblast, B lymphocyte or melanoma cell lines. We present the first demonstration that these isoforms originate from alternative translation initiation codons. We finally show that CIITA isoforms translocate to the nucleus with an apparently similar efficiency. Our data therefore demonstrate the existence of CIITA isoforms whose respective ratio depends on the cell type examined. However, we present evidence for a modulation of this ratio in a melanoma cell line with an abnormal constitutive expression of MHC class II molecules.
Barbieri
Giovanna
G
INSERM U396, Centre de Recherches Biomédicales des Cordeliers and Laboratoire d'Immunologie et d'Histocompatibilité, APHP, Hôpital St Louis, 75270 Paris, France.
Deffrennes
Virginie
V
Prod'homme
Thomas
T
Vedrenne
Jocelyn
J
Baton
Fabrice
F
Cortes
Claudio
C
Fischer
Alain
A
Bono
Maria-Rosa
MR
Lisowska-Grospierre
Barbara
B
Charron
Dominique
D
Alcaïde-Loridan
Catherine
C
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D006681:HLA-D Antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D007371:Interferon-gamma