Association of Stat3-dependent transcriptional activation of p19INK4D with IL-6-induced growth arrest.
Signal transducer and activator of transcription 3 (Stat3) is the major mediator of the IL-6-induced signals regulating growth and differentiation. In the M1 myeloleukemic cell line, Stat3 is a critical transcription factor causing repression of c-myc and c-myb genes, expression of junB and IRF1, growth arrest at G1, and subsequent macrophage differentiation. To understand the mechanisms by which Stat3 causes such effects, we searched for other Stat3-regulated genes possibly involved in growth arrest. We identified this inducible molecule as p19INK4D using a specific antibody. Both p19INK4D mRNA and protein were rapidly induced by IL-6 treatment without requiring de novo protein synthesis and the induction was fully suppressed by dominant-negative forms of Stat3. Thus both Stat3-regulated events, repressions of c-myc and c-myb and induction of p19INK4D, are likely to be involved in IL-6-induced growth arrest in M1 cells.
Narimatsu
M
M
Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Nakajima
K
K
Ichiba
M
M
Hirano
T
T
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; C493975:Cdkn2d protein, mouse; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases