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Molecular and Cellular Biology, July 1999, p. 5106-5112, Vol. 19, No. 7
Laboratory of Molecular Cell Biology, The
Rockefeller University, New York, New York 10021
Received 17 November 1998/Returned for modification 20 January
1999/Accepted 5 April 1999
Upon binding of gamma interferon (IFN-
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Linker Domain of Stat1 Is Required for Gamma
Interferon-Driven Transcription
) to its receptor, the
latent transcription factor Stat1 becomes phosphorylated, dimerizes, and enters the nucleus to activate transcription. In response to
IFN-
, Stat1 binds to Stat2 in a heterodimer that recruits p48, an
IRF family member, to activate transcription. A number of functional
domains of the STATs, including a C-terminal transactivation domain, a
dimerization domain, and an SH2 domain, are known. However, the highly
conserved residues between the DNA binding and SH2 domains (463 to
566), recently christened the linker domain on the basis of
crystallographic studies, have remained without a known function. In
the present study, we report that KE544-545AA point mutants in Stat1
abolish transcriptional responses to IFN-
but not to IFN-
. We
further show that this mutant Stat1 undergoes normal phosphorylation,
nuclear translocation, and DNA binding. Taken together with recent
structural evidence, these results suggest that the linker domain acts
as a critical contact point during the construction of a Stat1-driven
transcriptional complex.
*
Corresponding author. Mailing address: Laboratory of
Molecular Cell Biology, The Rockefeller University, 1230 York Ave., Box 167, New York, NY 10021. Phone: (212) 327-8791. Fax: (212) 327-8801. E-mail: darnell{at}rockvax.rockefeller.edu.
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