Two separate signal transducer and activator of transcription proteins regulate transcription of the serine proteinase inhibitor-3 gene in hepatic cells.
The serine proteinase inhibitor (SPI-3) gene expression is transcriptionally regulated by interleukin (IL)-6 and glucocorticoids in hepatic cells. To identify the transcription factors involved in regulation of the SPI-3 promoter-chloramphenicol acetyltransferase constructs we overexpressed Signal Transducer and Activator of Transcription (STAT) proteins (STAT1, STAT3, STAT5B, and STAT6) and CAAT enhancer-binding protein beta. Specific signaling pathways were activated by cointroduced receptors for growth hormone, IL-3, IL-4, or chimeric receptors containing the cytoplasmic domain of gp130. STAT3 and STAT5B induced transcription via the SPI-3 promoter. The STAT5B response was substantially enhanced by truncation of the 5'-flanking region from -1021 to -148. The responsiveness to STAT3 and STAT5B required the STAT binding element at -132 to -124. This element was sufficient to confer regulation onto a heterologous promoter gene construct. In contrast, overexpression of CAAT enhancer-binding protein beta reduced the transcriptional activity of the SPI-3 promoter, presumably by interfering with STAT protein binding to the promoter element. The SPI-3 gene is the first example of an acute phase gene that is responsive to both STAT3 and STAT5B.
Kordula
T
T
Department of Biochemistry and Molecular Biology, The University of Georgia, Athens, Georgia 306022, USA.
Ripperger
J
J
Morella
K M
KM
Travis
J
J
Baumann
H
H
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D050822:Cytokine Receptor gp130; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008894:Milk Proteins; D008969:Molecular Sequence Data; D051381:Rats; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D015703:Antigens, CD; D017931:DNA Primers; D004268:DNA-Binding Proteins; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D008894:Milk Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015842:Serine Proteinase Inhibitors; C494088:Stat3 protein, rat; C494097:Stat5b protein, rat; D015534:Trans-Activators; D050822:Cytokine Receptor gp130