Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex.

作者：S J Kim, Peter E. Angel, R Lafyatis, Kazue Hattori, Ki-Yong Kim, Michael B. Sporn, Michael Karin, Anita B. Roberts · 发表于：Molecular and Cellular Biology · 年份：1990 · DOI：10.1128/mcb.10.4.1492 · 被引用次数：644 · 研究领域：TGF-β signaling in diseases、Growth Hormone and Insulin-like Growth Factors、Kruppel-like factors research

The multifunctional actions of transforming growth factor beta 1 (TGF-beta 1) indicate that it has a pivotal control function in many physiological and pathological processes. An important property of TGF-beta 1 is its ability to activate its own mRNA expression and thereby increase its own secretion. Two distinct regions of the promoter of the TGF-beta 1 gene are responsive to autoregulation: one 5' to the upstream transcriptional start site and another located between the two major start sites. In both promoter regions, autoinduction is mediated by binding of the AP-1 (Jun-Fos) complex. An important contribution to this positive regulation is the autoactivation of c-jun transcription by AP-1. Cotransfection of antisense c-jun or antisense c-fos expression vectors prevents TGF-beta 1 autoinduction. These results demonstrate that both components of the AP-1 complex are required for TGF-beta 1 autoinduction. Induction of jun expression by TGF-beta 1, as well as jun autoinduction, may amplify the action of TGF-beta 1 during normal development and oncogenesis.