Nuclear import of hnRNP A1 is mediated by a novel cellular cofactor related to karyopherin-beta.

Journal Article (Journal Article)

Heterogeneous nuclear ribonucleoprotein A1 contains a sequence, termed M9, that functions as a potent nuclear localization signal (NLS) yet bears no similarity to the well-defined basic class of NLSs. Here, we report the identification of a novel human protein, termed MIP, that binds M9 specifically both in vivo and in vitro yet fails to interact with non-functional M9 point mutants. Of note, the 101 kDa MIP protein bears significant homology to human karyopherin/importin-beta, a protein known to mediate the function of basic NLSs. The in vitro nuclear import of a protein substrate containing the M9 NLS was found to be dependent on provision of the MIP protein in trans. Cytoplasmic microinjection of a truncated form of MIP that retains the M9 binding site blocked the in vivo nuclear import of a substrate containing the M9 NLS yet failed to affect the import of a similar substrate bearing a basic NLS. These data indicate that nuclear import of hnRNP A1 is mediated by a novel cellular import pathway that is distinct from, yet evolutionarily related to, the pathway utilized by basic NLS sequences.

Full Text

Duke Authors

Cited Authors

  • Fridell, RA; Truant, R; Thorne, L; Benson, RE; Cullen, BR

Published Date

  • June 1997

Published In

Volume / Issue

  • 110 ( Pt 11) /

Start / End Page

  • 1325 - 1331

PubMed ID

  • 9202393

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.110.11.1325


  • eng

Conference Location

  • England