Association of Stat3-dependent transcriptional activation of p19INK4D with IL-6-induced growth arrest

Biochem Biophys Res Commun. 1997 Sep 29;238(3):764-8. doi: 10.1006/bbrc.1997.7387.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Cell Cycle Proteins*
  • Cell Division / drug effects
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase Inhibitor p16*
  • Cyclin-Dependent Kinase Inhibitor p19
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Growth Inhibitors / pharmacology*
  • Interleukin-6 / pharmacology*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Mice
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins*
  • Retinoblastoma Protein / metabolism
  • STAT3 Transcription Factor
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcriptional Activation* / drug effects
  • Tumor Cells, Cultured


  • Carrier Proteins
  • Cdkn2d protein, mouse
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p19
  • DNA-Binding Proteins
  • Growth Inhibitors
  • Interleukin-6
  • Proto-Oncogene Proteins
  • Retinoblastoma Protein
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases