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Related Experiment Videos

Molecular chaperones function as steroid receptor nuclear mobility factors.

Cem Elbi1, Dawn A Walker, Guillermo Romero

  • 1Laboratory of Receptor Biology and Gene Expression, Building 41, Room B602, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA.

Proceedings of the National Academy of Sciences of the United States of America
|February 24, 2004
PubMed
Summary

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Molecular chaperones orchestrate steroid hormone receptor nuclear trafficking. This study identifies soluble factors and reveals chaperones regulate glucocorticoid and progesterone receptor mobility and function within the nucleus.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Steroid hormone receptors exhibit rapid nuclear mobility and dynamic exchange at target sites.
  • Soluble factors governing nuclear trafficking of these receptors remain largely unidentified.

Purpose of the Study:

  • To identify soluble factors responsible for nuclear trafficking of steroid hormone receptors.
  • To investigate the role of molecular chaperones in regulating steroid receptor nuclear mobility and function.

Main Methods:

  • Developed a novel in situ subnuclear trafficking assay using transcriptionally active nuclei depleted of soluble factors.
  • Employed fluorescence recovery after photobleaching (FRAP) to measure receptor mobility.
  • Utilized geldanamycin to inhibit heat-shock protein 90 chaperone activity.

Related Experiment Videos

  • Assessed mobility recovery using purified chaperone and cochaperone proteins.

    • Main Results:

    • Nuclear mobility of glucocorticoid receptor (GR) recovered upon addition of reticulocyte lysate, but was inhibited by geldanamycin.
    • ATP-dependent recovery of nuclear mobility for GR and progesterone receptor (PR) was observed with purified chaperones/cochaperones.
    • Hormone presence during recovery retarded the nuclear mobility of both GR and PR.

    Conclusions:

    • Identified soluble nuclear mobility factors involved in steroid receptor trafficking.
    • Demonstrated a novel regulatory role for molecular chaperones in steroid receptor nuclear mobility and function.
    • Showcased hormone-dependent modulation of steroid receptor nuclear transport.