RGD Reference Report - Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation. - Rat Genome Database

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Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation.

Authors: McInerney, EM  Rose, DW  Flynn, SE  Westin, S  Mullen, TM  Krones, A  Inostroza, J  Torchia, J  Nolte, RT  Assa-Munt, N  Milburn, MV  Glass, CK  Rosenfeld, MG 
Citation: McInerney EM, etal., Genes Dev. 1998 Nov 1;12(21):3357-68.
RGD ID: 2293532
Pubmed: PMID:9808623   (View Abstract at PubMed)
PMCID: PMC317227   (View Article at PubMed Central)

Ligand-dependent activation of gene transcription by nuclear receptors is dependent on the recruitment of coactivators, including a family of related NCoA/SRC factors, via a region containing three helical domains sharing an LXXLL core consensus sequence, referred to as LXDs. In this manuscript, we report receptor-specific differential utilization of LXXLL-containing motifs of the NCoA-1/SRC-1 coactivator. Whereas a single LXD is sufficient for activation by the estrogen receptor, different combinations of two, appropriately spaced, LXDs are required for actions of the thyroid hormone, retinoic acid, peroxisome proliferator-activated, or progesterone receptors. The specificity of LXD usage in the cell appears to be dictated, at least in part, by specific amino acids carboxy-terminal to the core LXXLL motif that may make differential contacts with helices 1 and 3 (or 3') in receptor ligand-binding domains. Intriguingly, distinct carboxy-terminal amino acids are required for PPARgamma activation in response to different ligands. Related LXXLL-containing motifs in NCoA-1/SRC-1 are also required for a functional interaction with CBP, potentially interacting with a hydrophobic binding pocket. Together, these data suggest that the LXXLL-containing motifs have evolved to serve overlapping roles that are likely to permit both receptor-specific and ligand-specific assembly of a coactivator complex, and that these recognition motifs underlie the recruitment of coactivator complexes required for nuclear receptor function.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ncoa1Ratcellular response to hormone stimulus  IMP  RGD 
Ncoa1Ratresponse to estradiol  IMP  RGD 
Ncoa1Ratresponse to progesterone  IMP  RGD 
Ncoa1Ratresponse to retinoic acid  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ncoa1  (nuclear receptor coactivator 1)


Additional Information