Human topoisomerase II α nuclear export is mediated by two CRM - 1 - dependent nuclear export signals

Recent investigations have elucidated several molecular pathways for the nuclear import and export of proteins (Kau and Silver, 2003; Weis, 2003) across transport passageways or nuclear pore complexes (NPCs) (Dreger, 2003). The NPC is a large (125 MDa) multimeric protein structure that perforates the nuclear envelope and channels proteins greater than 60 kDa into or out of the nucleus. The constituents of the NPC have been described in yeast (Rout et al., 2000) and mammalian cells (Cronshaw et al., 2002). Proteins targeted for receptor-mediated transport across the NPC must either contain a nuclear localization signal (NLS) or a nuclear export signal (NES). Protein NLS are typically short clusters of basic amino acids, often preceded by an acidic amino acid or proline residue. However, a NLS may also consist of bipartite clusters of basic amino acids separated by a spacer region of approximately ten amino acids, often flanked by a neutral or acidic amino acid. Previously described NLSs are annotated in SWISS-PROT (Bairoch and Apweiler, 2000) and PIR (Wu et al., 2002), and can be retrieved at the NLS database located at the Predict NLS server (Cokol et al., 2000). Protein NES are hydrophobic rich sequences that have a characteristic spacing of leucine, isoleucine, valine, and/or phenylalanine. To date, approximately 75 experimentally validated protein-NES have