Amino-terminal signal transducer and activator of transcription (STAT) domains regulate nuclear translocation and STAT deactivation.
The first approximately 100 amino acids of the STAT (signal transducer and activator of transcription) family of transcription factors share a high degree of sequence similarity. To determine whether they encode a functionally conserved domain, amino-terminal chimeric STATs were created. These chimeric STATs share a number of properties with wild-type Stat1, including a predominately cytoplasmic pattern of expression in unstimulated cells. Upon stimulation with ligand, the chimeric STATs rapidly become tyrosine-phosphorylated, dimerize, and are able to bind DNA. They are also able to heterodimerize with coexpressed wild-type Stat1. Yet in contrast to wild-type Stat1, the chimeric STATs exhibit a marked defect in deactivation. Moreover, the persistence of active chimeras correlates directly with an inability to translocate to the nucleus. The defects both in nuclear translocation and in deactivation are rescued by heterodimerization with coexpressed wild-type Stat1. This study indicates that STAT amino termini provide a signal that is important for nuclear translocation and, subsequently, deactivation. It also suggests that deactivation may depend on a prior nuclear localization event.
Strehlow
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I
Departments of Microbiology and Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Schindler
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C
D000595:Amino Acid Sequence; D001692:Biological Transport; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D010744:Phosphoric Monoester Hydrolases; D019311:Staurosporine