A Phorbol Ester-Regulated Ribonuclease System Controlling Transforming Growth Factor β1 Gene Expression in Hematopoietic Cells

Abstract

12-Tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of U937 promonocytes leads to a 30-fold increase in transforming growth factor β1 (TGF-β1) gene expression, and this effect results from a stabilized mRNA. Similar up-regulation was detected in TPA-treated K562 erythroblasts but was absent from cell lines that do not differentiate in response to TPA. Related studies in vitro showed that postnuclear extracts of U937 promonocytes contain a ribonuclease system that degrades TGF-β1 mRNA selectively and that this system is completely blocked by prior treatment of the cells with TPA. These data identify a new mechanism for regulating TGF-β1 mRNA levels and allow us to establish the overall basis for control of TGF-β1 gene expression by activation of protein kinase C. Our results also provide a new basis for understanding the long-term up-regulation of TGF-β1 gene expression that can accompany hematopoietic cell differentiation.