[HTML][HTML] A signature motif in transcriptional co-activators mediates binding to nuclear receptors

DM Heery, E Kalkhoven, S Hoare, MG Parker - Nature, 1997 - nature.com
DM Heery, E Kalkhoven, S Hoare, MG Parker
Nature, 1997nature.com
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 (,) …
Abstract
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.
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