Protein Nuclear Import is Modulated by Calreticulin

Abstract

Alarge number of cellular events occur following the import of proteins into the nucleus from the cytoplasm. Numerous studies have identified protein sequences which act as a signal for protein import into the nucleus.1–3 Although a specific consensus nuclear signal sequence for protein nuclear import has not been identified, the nuclear localization signal (NLS) usually consists of clusters of arginines, lysines and a helix destabilizing amino acid such as proline or glycine.4–7 The NLS sequence of SV-40 large T antigen (P-K-K-K-R-K-V) is one example of the prototype of a NLS. The mutation of the second lysine to threonine greatly reduces nuclear import. Some proteins contain split or bipartite NLS with spacer sequences between the NLS sequences. Nucleoplasmin, which contains two clusters of basic amino acids separated by a 10 residue long spacer sequence, is one example of a protein containing a bipartite NLS.8–10 Some proteins do not contain their own NLS but are shuttled into the nucleus by another protein containing a NLS.11 Many proteins contain more than one NLS.12–15 The position of the NLS signal in the protein is important for nuclear import. Protein import does not occur when the NLS is buried in the interior of the protein.16