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Cited by 613

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation

Open access
McInerney, Eileen M., Rose, David W., Flynn, Sarah E., Westin, Stefan, Mullen, Tina-Marie, Krones, Anna, Inostroza, Juan, Torchia, Joseph, Nolte, Robert T., Assa-Munt, Nuria, Milburn, Michael V., Glass, Christopher K., Rosenfeld, Michael G.·1998·Genes & Development
DOI 10.1101/gad.12.21.3357
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Abstract

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 PPARγ 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.

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Metadata

Authors
McInerney, E. M., Rose, D. W., Flynn, S. E., Westin, S., Mullen, T.-M., Krones, A., Inostroza, J., Torchia, J., Nolte, R. T., Assa-Munt, N., Milburn, M. V., Glass, C. K., & Rosenfeld, M. G.
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
1998-11-01
Volume
12
Issue
21
Pages
3357-3368
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.12.21.3357
OpenAlex
W2141686420
Cited by
613
References
5
Type
posted content
Language
en
Open access
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