CRM1 mediates nuclear export of nonstructural protein 2 from parvovirus minute virus of mice

The nonstructural protein 2 (NS2) from parvovirus minute virus of mice (MVM p) is a 25-kDa polypeptide which localizes preferentially to the cytoplasm and associates with cellular proteins in cytoplasm. These lines of evidence suggest that NS2 is positively exported from the nucleus to cytoplasm and functions in cytoplasm. We report here that nuclear export of NS2 is inhibi ted by leptomycin B (LMB), a drug that specifically blocks nuclear export s ignal (NES)-chromosomal region maintenance 1 (CRM1) interactions. CRM1 bind s specifically to the 81- to 106-amino-acid (aa) region of NS2, and the reg ion of NS2 actually functions as a NES. Interestingly, this region appears to be distinct from a typical NES sequence, which consists of leucine-rich sequences. These results indicate that NS2 protein is continuously exported from the nucleus by a CRM1-dependent mechanism and suggest that CRM1 also exports to distinct type of NESs. (C) 1999 Academic Press.