Open AccessUpregulation of STAT1 protein in cells lacking or expressing mutants of the double‐stranded RNA‐dependent protein kinase PKR
Author(s) -
Tam Nancy Wai Ning,
Ishii Tetsu,
Li Suiyang,
Wong Andrew HoiTao,
Cuddihy Andrew R.,
Koromilas Antonis E.
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00360.x
Subject(s) - protein kinase r , stat1 , biology , interferon , downregulation and upregulation , microbiology and biotechnology , signal transduction , eif 2 kinase , stat protein , activator (genetics) , protein kinase a , phosphorylation , gene , stat3 , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , virology , genetics
The interferon (IFN)‐inducible double‐stranded (ds) RNA‐dependent protein kinase PKR plays a role in the regulation of gene expression through its capacity to phosphorylate the translation initiation factor eIF‐2 and to inhibit protein synthesis. In addition to translational control, PKR has been implicated in the regulation of gene expression at the transcriptional level. In this regard, we have reported that PKR participates in IFN‐and dsRNA‐mediated signaling pathways by interacting with and modulating the transcriptional activity of the signal transducer and activator of transcription STAT1 [Wong, A.H.‐T., Tam, N.W.N., Yang, Y.‐L., Cuddihy, A.R., Li, S., Kirchhoff, S., Hauser, H., Decker, T. & Koromilas, A.E. (1997) EMBO J . 16 , 1291–1304]. Here we report that the STAT1 protein is upregulated in cells lacking PKR (PKR −/– ) and in cells expressing dominant negative PKR mutants. This upregulation is specific for STAT1 as increased expression is not observed for other STAT proteins. The inhibitory effect of PKR on STAT1 expression is exerted at the post‐translational level because PKR −/– cells exhibit higher STAT1 protein stability than PKR +/+ cells.