Modulation of nuclear protein import: a novel means of regulating gene expression.
Eukaryotic cells depend upon the regulated exchange of proteins and RNA between the cytoplasm and the nucleus for survival. Various cytoplasmic and nuclear proteins play a fundamental role in this specific transport process. Over the last few years the components and stages of nuclear protein transport have been characterized in significant detail. Because many of the proteins that are transported into the nucleus are transcription factors, the import process is an interesting target for the manipulation of gene expression. Over time the eukaryotic cell has assembled a number of methods by which to regulate the nuclear localization of transcription factors. Within the last few years, there have been several reports of the pharmacologic manipulation of the localization of nuclear proteins as well. In addition, a recent study suggests that viruses are able to modulate host cell nuclear protein transport in vivo. This report will present an overview of nuclear protein import, describe the various in vivo mechanisms by which the cell regulates this process, and discuss recent attempts to manipulate the process with small molecule compounds. As nuclear import is a fundamental cellular process, potential opportunities for the future may arise from direct and specific ways to modulate this process and thereby treat diseases characterized by dysregulation of transcription factor activity.
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
S M
SM
Fujihara
S G
SG
Nadler
D000818:Animals; D001692:Biological Transport; D015967:Gene Expression Regulation, Viral; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
D009687:Nuclear Proteins