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PMID: 2108318 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 10 ·No. 4 ·1990-04-00 ·Pages 1492-7

Kim SJ, Angel P, Lafyatis R, Hattori K, Kim KY, Sporn MB, Karin M, Roberts AB

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.

MeSH Terms
Adenocarcinoma Cell Line DNA-Binding Proteins/biosynthesis,genetics Enzyme Induction Gene Expression Homeostasis Humans Lung Neoplasms Plasmids Promoter Regions, Genetic Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins/biosynthesis,genetics Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Proto-Oncogenes RNA, Messenger/genetics Restriction Mapping Transcription Factors/biosynthesis,genetics Transcription, Genetic Transforming Growth Factors/biosynthesis,genetics,physiology Tumor Cells, Cultured/metabolism
Chemicals
DNA-Binding Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun RNA, Messenger Transcription Factors Transforming Growth Factors Protein-Tyrosine Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kim S J
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Angel P
Lafyatis R
Hattori K
Kim K Y
Sporn M B
Karin M
Roberts A B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.10.4.1492-1497.1990
Published
1990-04-00
Pages
1492-7
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC362252
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.10.4.1492-1497.1990 PMC Full Text View journal details
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