Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex.
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.
Kim
S J
SJ
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Angel
P
P
Lafyatis
R
R
Hattori
K
K
Kim
K Y
KY
Sporn
M B
MB
Karin
M
M
Roberts
A B
AB
D000230:Adenocarcinoma; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D008175:Lung Neoplasms; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D015291:Transforming Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D015291:Transforming Growth Factors; D011505:Protein-Tyrosine Kinases