A signature motif in transcriptional co-activators mediates binding to nuclear receptors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-06

AUTHORS

David M. Heery, Eric Kalkhoven, Susan Hoare, Malcolm G. Parker

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. More... »

PAGES

733-736

Journal

TITLE

Nature

ISSUE

6634

VOLUME

387

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/42750

    DOI

    http://dx.doi.org/10.1038/42750

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1025234467

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9192902


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