Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA.
Proteins containing AT hooks bind A/T-rich DNA through a nine-amino-acid motif and are thought to co-regulate transcription by modifying the architecture of DNA, thereby enhancing the accessibility of promoters to transcription factors. Here we describe AKNA, a human AT-hook protein that directly binds the A/T-rich regulatory elements of the promoters of CD40 and CD40 ligand (CD40L) and coordinately regulates their expression. Consistent with its function, AKNA is a nuclear protein that contains multiple PEST protein-cleavage motifs, which are common in regulatory proteins with high turnover rates. AKNA is mainly expressed by B and T lymphocytes, natural killer cells and dendritic cells. During B-lymphocyte differentiation, AKNA is mainly expressed by germinal centre B lymphocytes, a stage in which receptor and ligand interactions are crucial for B-lymphocyte maturation. Our findings show that an AT-hook molecule can coordinately regulate the expression of a key receptor and its ligand, and point towards a molecular mechanism that explains homotypic cell interactions.
Department of Immunology, Box 178, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
A
A
Siddiqa
J C
JC
Sims-Mourtada
L
L
Guzman-Rojas
R
R
Rangel
C
C
Guret
V
V
Madrid-Marina
Y
Y
Sun
H
H
Martinez-Valdez
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
C423232:AKNA protein, human; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D023201:CD40 Ligand; D004247:DNA