Nuclear export signal located within theDNA-binding domain of the STAT1transcription factor.
Latent signal transducers and activators of transcription (STATs) reside in the cytoplasm but rapidly accumulate in the nucleus following cytokine stimulation. Nuclear accumulation requires specific tyrosine phosphorylation and STAT dimerization. The presence of STATs in the nucleus is transient, however, and within hours the STATs reappear in the cytoplasm. Results indicate that STAT1 can be dephosphorylated in the nucleus and actively exported by the chromosome region maintenance 1 (CRM1) export receptor. CRM1 recognizes a specific amino acid sequence located within the DNA-binding domain of STAT1. This region shares sequence and functional properties of characterized nuclear export signals. The location of this sequence within STAT1 suggests that it is not accessible to CRM1 when STAT1 is bound to DNA. Evidence is presented to support a model in which STAT1 is tyrosine dephosphorylated in the nucleus and dissociates from DNA, allowing recognition by CRM1 and nuclear export. The regulated export of STAT1 may contribute to silencing of the signal pathway and/or to re-establish STAT1 in the cytoplasm to monitor activity of receptor-kinase signals.
McBride
K M
KM
Department of Pathology, SUNY at Stony Brook, Stony Brook, NY 11794, USA.
McDonald
C
C
Reich
N C
NC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D049452:Green Fluorescent Proteins; D006801:Humans; D028884:Karyopherins; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D019913:Nuclear Localization Signals; D015345:Oligonucleotide Probes / Q000235:genetics; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D049452:Green Fluorescent Proteins; D028884:Karyopherins; D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D015345:Oligonucleotide Probes; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000097606:Exportin 1 Protein; C494079:STAT1 protein, human