TRANSCRIPTIONAL ACTIVATION OF THE IL-6 RESPONSE ELEMENT IN THE JUNB PROMOTER IS MEDIATED BY MULTIPLE STAT FAMILY PROTEINS

IL-6 signals activate an IL-6 response element in the junB promoter, J RE-IL6, in a Ras-independent manner. IL-6 rapidly induced a DNA-bindin g activity to the Ets binding site of JRE-IL6 (JEBS), one of necessary DNA motifs of the IL-6 response element. The IL-6-induced JEBS-bindin g activity was indistinguishable from those to acute phase response el ement (APRE) in both kinetics of induction and its DNA-binding specifi city. Purified APRE binding factors (APRFs) from IL-6-stimulated rat l iver were found to be composed of multiple Stat3-related proteins and Stat1. Moreover the purified APRFs specifically made a complex with JR E-IL6 with the same mobility as that observed in the crude extracts. T hese results indicate that an immediate early signal of IL-6 leading t o activation of JRE-IL6 is mediated by STAT family transcription facto rs. (C) 1994 Academic Press, Inc.