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Regulated nuclear import of the STAT1 transcription factor by direct binding of importin‐α
Author(s) -
McBride Kevin M.,
Banninger Gregg,
McDonald Christine,
Reich Nancy C.
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.7.1754
Subject(s) - importin , biology , transcription factor , nuclear transport , transcription (linguistics) , dna binding protein , microbiology and biotechnology , genetics , cell nucleus , nucleus , gene , linguistics , philosophy
Signal transducers and activators of transcription (STATs) reside in a latent state in the cytoplasm of the cell, but accumulate in the nucleus in response to cytokines or growth factors. Localization in the nucleus occurs following STAT tyrosine phosphorylation and dimerization. In this report we demonstrate a direct interaction of importin‐α5 with tyrosine‐phosphorylated STAT1 dimers, and provide evidence that a nuclear localization signal (NLS) exists in an inactive state within a STAT1 monomer. A mutation in STAT1 leucine 407 (L407A) is characterized, which generates a protein that is accurately tyrosine phosphorylated in response to interferon, dimerizes and binds DNA, but does not localize to the nucleus. The import defect of STAT1(L407A) appears to be a consequence of the inability of this protein to be recognized by its import shuttling receptor. In addition, we demonstrate that STAT1 binding to specific target DNA effectively blocks importin‐α5 binding. This result may play a role in localizing STAT1 to its destination in the nucleus, and in releasing importin‐α5 from STAT1 for recycling back to the cytoplasm.