Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos.
A complementary DNA encoding a member of the leucine-zipper class of proteins (human X-box-binding protein, hXBP-1) that binds to the 3' end of the conserved X box (X2) of the HLA-DRA major histocompatibility complex gene was recently described. Further gel-retardation analysis has demonstrated that hXBP-1 also binds to HLA-DPB X2 but not to other X2 sequences. Transient transfection of a mammalian expression vector with the hXBP-1 cDNA inserted in the antisense orientation represses the surface expression of HLA-DR and HLA-DP in Raji cells. Cotransfection of the antisense hXBP-1 vector with a HLA-DRA/chloramphenicol acetyltransferase (but not a HLA-DQB/chloramphenicol acetyltransferase) reporter plasmid decreases chloramphenicol acetyltransferase activity in Raji cells and in gamma-interferon-treated HeLa cells relative to cells cotransfected with a control antisense vector. Moreover, hXBP-1 is shown to form a stable heterodimer with the product of the c-fos protooncogene. These data suggest that the hXBP-1 c-fos heterodimer is critical for the transcription of a subset of the human class II major histocompatibility complex genes and that the regulatory mechanisms for the different class II genes are distinct.
Ono
S J
SJ
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Liou
H C
HC
Davidon
R
R
Strominger
J L
JL
Glimcher
L H
LH
D016375:Antisense Elements (Genetics); D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006682:HLA-DP Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007163:Immunosorbent Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D016375:Antisense Elements (Genetics); D004268:DNA-Binding Proteins; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D004247:DNA