KAP1 regulates type I interferon/STAT1-mediated IRF-1 gene expression.
Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal co-repressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN)/STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulator of the IFN/STAT1 signaling pathway.
Kamitani
Shinya
S
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.
Ohbayashi
Norihiko
N
Ikeda
Osamu
O
Togi
Sumihito
S
Muromoto
Ryuta
R
Sekine
Yuichi
Y
Ohta
Kazuhide
K
Ishiyama
Hironobu
H
Matsuda
Tadashi
T
D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D007370:Interferon Type I / Q000378:metabolism* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation; D000076183:Tripartite Motif-Containing Protein 28
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28; D006655:Histone Deacetylases