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Heterokaryon Technique for Analysis of Cell Type-specific Localization
Published on: March 11, 2011
DNA binding domains in diverse nuclear receptors function as nuclear export signals
B E Black1, J M Holaska, F Rastinejad
1Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
Current Biology : CB
|November 24, 2001
Summary
The DNA binding domain (DBD) of the glucocorticoid receptor (GR) acts as a nuclear export signal (NES), mediating a common export pathway for nuclear receptors. This DBD-mediated export, along with NLS-mediated import, regulates receptor shuttling and activity.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Nuclear receptors are transcription factors regulating gene expression.
- Nuclear import utilizes nuclear localization signals (NLS) and importins.
- Nuclear receptors lack typical NES and Crm1-mediated export pathways.
Purpose of the Study:
- To identify the nuclear export signal (NES) in the glucocorticoid receptor (GR).
- To characterize the nuclear export pathway for nuclear receptors.
Main Methods:
- Mutational analysis of the GR DNA binding domain (DBD).
- Alanine-scanning mutagenesis to identify critical residues.
- Assessing nuclear export function using a GFP reporter protein.
Main Results:
- The GR's 69 amino acid DBD is necessary and sufficient for nuclear export.
- A 15 amino acid sequence within the GR-DBD functions as an NES.
- DBDs from ten different nuclear receptors also function as export signals.
- Nuclear export mediated by the DBD is saturable.
Conclusions:
- Nuclear receptors share a common pathway for nuclear export.
- A shuttling cycle of NLS-mediated import and DBD-mediated export integrates receptor compartmentalization and activity.
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