The ins and outs of STAT1 nuclear transport.
There is an inherent elegance in being in the right place at the right time. The STAT1 transcription factor possesses regulatory signals that ensure its distribution to the right cellular location at the right time. Latent STAT1 resides primarily in the cytoplasm, and there it responds to hormone signaling through tyrosine phosphorylation by Janus kinases or growth factor receptors. After phosphorylation, STAT1 dimerizes, and this conformational change reveals a nuclear import signal that is recognized by a specific nuclear import carrier. In the nucleus, the STAT1 dimer dissociates from the import carrier and binds to specific DNA target sites in the promoters of regulated genes. STAT1 is subsequently dephosphorylated in the nucleus by a constitutively active tyrosine phosphatase, leading to its dissociation from DNA. A nuclear export signal of STAT1 appears to be masked when dimers are bound to DNA, but it becomes accessible to the CRM1 export carrier after dissociation from DNA. CRM1 binds STAT1 and transports the transcription factor back to the cytoplasm. Studies show that the regulatory trafficking signals that guide the nuclear import and export of STAT1 reside within its DNA binding domain. The location of these signals indicates that their function has coevolved with the ability of STAT1 to bind DNA and regulate gene expression. The nuclear import and subsequent recycling of STAT1 to the cytoplasm are integral to its function as a signal transducer and activator of transcription.
McBride
Kevin M
KM
Department of Pathology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Reich
Nancy C
NC
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators