A signature motif in transcriptional co-activators mediates binding to nuclear receptors.

The binding of lipophilic hormones, retinoids and vitamins to members of the nuclear-receptor superfamily modifies the DNA-binding and transcriptional properties of these receptors, resulting in the activation or repression of target genes. Ligand binding induces conformational changes in nuclear receptors and promotes their association with a diverse group of nuclear ...
proteins, including SRC-1/p160, TIF-2/GRIP-1 and CBP/p300 which function as co-activators of transcription, and RIP-140, TIF-1 and TRIP-1/SUG-1 whose functions are unclear. Here we report that a short sequence motif LXXLL (where L is leucine and X is any amino acid) present in RIP-140, SRC-1 and CBP is necessary and sufficient to mediate the binding of these proteins to liganded nuclear receptors. We show that the ability of SRC-1 to bind the oestrogen receptor and enhance its transcriptional activity is dependent upon the integrity of the LXXLL motifs and on key hydrophobic residues in a conserved helix (helix 12) of the oestrogen receptor that are required for its ligand-induced activation function. We propose that the LXXLL motif is a signature sequence that facilitates the interaction of different proteins with nuclear receptors, and is thus a defining feature of a new family of nuclear proteins.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, CREB-Binding Protein, Conserved Sequence, DNA, Histone Acetyltransferases, Humans, Ligands, Mice, Nuclear Proteins, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 2, Protein Structure, Secondary, Receptors, Cytoplasmic and Nuclear, Receptors, Estrogen, Recombinant Fusion Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection
Date: Jun. 12, 1997
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