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. 1990 Apr;10(4):1492–1497. doi: 10.1128/mcb.10.4.1492

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

S J Kim 1, P Angel 1, R Lafyatis 1, K Hattori 1, K Y Kim 1, M B Sporn 1, M Karin 1, A B Roberts 1
PMCID: PMC362252  PMID: 2108318

Abstract

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.

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