ASSOCIATION OF STAT3-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF P19(INK4D) WITH IL-6-INDUCED GROWTH ARREST

Signal transducer and activator of transcription 3 (Stat3) is the majo r mediator of the IL-6-induced signals regulating growth and different iation. In the M1 myeloleukemic cell line, Stat3 is a critical transcr iption factor causing repression of c-myc and c-myb genes, expression of junB and IRF1, growth arrest at G1, and subsequent macrophage diffe rentiation. To understand the mechanisms by which Stat3 causes such ef fects, we searched for other Stat3-regulated genes possibly involved i n growth arrest, We identified this inducible molecule as p19(INK4D) u sing a specific antibody. Both p19(INK4D) mRNA and protein were rapidl y induced by IL-6 treatment without requiring de novo protein synthesi s and the induction was fully suppressed by dominant-negative forms of Stat3. Thus both Stat3-regulated events, repressions of c-myc and c-m yb and induction of p19(INK4D), are likely to be involved in IL-6-indu ced growth arrest in M1 cells. (C) 1997 Academic Press.