STAT3 is enriched in nuclear bodies.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is involved in a variety of biological functions. It is essential for the signal transduction of interleukin-6 (IL-6) and related cytokines. In response to IL-6 stimulation STAT3 becomes phosphorylated and translocates into the nucleus where it binds to enhancer sequences of target genes. We found that activated STAT3 is enriched in dot-like structures within the nucleus, which we termed STAT3 nuclear bodies. To examine the dynamics of STAT3 nuclear body formation, a fusion protein of STAT3 and yellow fluorescent protein (YFP) was constructed. Studies in living cells have shown that the appearance of STAT3 nuclear bodies is transient, correlating with the timecourse of tyrosine-phosphorylation of STAT3. Furthermore, we show by fluorescence recovery after photobleaching (FRAP) analysis that STAT3 within nuclear bodies consists of a highly mobile and an immobile fraction. Colocalization studies provided evidence that these bodies are accompanied with CREB binding protein (CBP) and acetylated histone H4, which are markers for transcriptionally active chromatin. Moreover, STAT3 nuclear bodies in HepG2 cells are not colocalized with promyelocytic leukemia oncoprotein (PML)-containing bodies; neither is a sumoylation of activated STAT3 detectable. Taken together, our data suggest that STAT3 nuclear bodies are either directly involved in active gene transcription or they serve as reservoirs of activated STAT3.
Herrmann
Andreas
A
Institut für Biochemie, Universitätsklinikum RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
Sommer
Ulrike
U
Pranada
Albert L
AL
Giese
Bernd
B
Küster
Andrea
A
Haan
Serge
S
Becker
W
W
Heinrich
Peter C
PC
Müller-Newen
Gerhard
G
D000818:Animals; D019556:COS Cells; D050882:CREB-Binding Protein; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D005786:Gene Expression Regulation / Q000502:physiology; D006657:Histones / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D025842:SUMO-1 Protein / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D015850:Interleukin-6; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; D025842:SUMO-1 Protein; D015534:Trans-Activators; D050882:CREB-Binding Protein