Nuclear import by karyopherin-βs: recognition and inhibition

Biochim Biophys Acta. 2011 Sep;1813(9):1593-606. doi: 10.1016/j.bbamcr.2010.10.014. Epub 2010 Oct 26.

Abstract

Proteins in the karyopherin-β family mediate the majority of macromolecular transport between the nucleus and the cytoplasm. Eleven of the 19 known human karyopherin-βs and 10 of the 14S. cerevisiae karyopherin-βs mediate nuclear import through recognition of nuclear localization signals or NLSs in their cargos. This receptor-mediated process is essential to cellular viability as proteins are translated in the cytoplasm but many have functional roles in the nucleus. Many known karyopherin-β-cargo interactions were discovered through studies of the individual cargos rather than the karyopherins, and this information is thus widely scattered in the literature. We consolidate information about cargos that are directly recognized by import-karyopherin-βs and review common characteristics or lack thereof among cargos of different import pathways. Knowledge of karyopherin-β-cargo interactions is also critical for the development of nuclear import inhibitors and the understanding of their mechanisms of inhibition. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Amino Acid Sequence
  • Humans
  • Karyopherins / chemistry
  • Karyopherins / genetics
  • Karyopherins / physiology
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Localization Signals / chemistry
  • Nuclear Localization Signals / genetics
  • Nuclear Localization Signals / physiology
  • Protein Interaction Domains and Motifs
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology
  • Signal Transduction / physiology
  • beta Karyopherins / chemistry
  • beta Karyopherins / genetics
  • beta Karyopherins / physiology*

Substances

  • Karyopherins
  • Nuclear Localization Signals
  • Saccharomyces cerevisiae Proteins
  • beta Karyopherins
  • transportin SR