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Molecular chaperones function as steroid receptor nuclear mobility factors. | LitMetric

Molecular chaperones function as steroid receptor nuclear mobility factors.

Proc Natl Acad Sci U S A

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

Published: March 2004

AI Article Synopsis

  • Live cell imaging shows that steroid hormone receptors move quickly within cell nuclei and exchange dynamically at active target sites, but it's unclear what factors control this movement.
  • Researchers created a new assay to study this nuclear mobility, finding that the presence of certain chaperones is essential for the movement of glucocorticoid (GR) and progesterone receptors (PR).
  • The study highlights the role of molecular chaperones in regulating how these steroid receptors function within the nucleus, especially in response to hormonal signals.

Article Abstract

Live cell imaging has revealed the rapid mobility of steroid hormone receptors within nuclei and their dynamic exchange at transcriptionally active target sites. Although a number of other proteins have been shown to be highly mobile within nuclei, the identity of soluble factors responsible for orchestrating nuclear trafficking remains unknown. We have developed a previously undescribed in situ subnuclear trafficking assay that generates transcriptionally active nuclei, which are depleted of soluble factors required for the nuclear mobility of glucocorticoid (GR) and progesterone receptors (PR). Using this system and a fluorescence recovery after photobleaching technique, we demonstrate that nuclear mobility of GR recovered on incubation with reticulocyte lysate was inhibited by geldanamycin, a drug that blocks the chaperone activity of heat-shock protein 90. Direct proof of molecular chaperone involvement in steroid receptor subnuclear trafficking was provided by the ATP-dependent recovery of nuclear mobility of GR and PR on incubation with various combinations of purified chaperone and/or cochaperone proteins. Additionally, for both receptors, the inclusion of hormone during the recovery period leads to a retardation of nuclear mobility. Thus, our results provide a description of soluble nuclear mobility factors and furthermore demonstrate a previously unrecognized role for molecular chaperones in the regulation of steroid receptor function within the nucleus.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC365713PMC
http://dx.doi.org/10.1073/pnas.0400116101DOI Listing

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