Related Experiment Videos
Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation
L Pertovaara1, L Sistonen, T J Bos
1Department of Virology and Pathology, University of Helsinki, Finland.
Abstract:
Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.
Insights
Transforming growth factor beta (TGF-β) rapidly enhances junB and c-jun gene expression in various cells, initiating a key part of its signal transduction pathway. This early genomic response involves jun transcription factors, potentially explaining TGF-β
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Transforming growth factor beta (TGF-β) is a crucial polypeptide regulating cell proliferation and differentiation.
- The precise molecular mechanisms of TGF-β signal transduction remain incompletely understood.
Purpose of the Study:
- To investigate the early molecular events in TGF-β signal transduction.
- To identify genes regulated by TGF-β and their role in cellular responses.
Main Methods:
- Analysis of junB and c-jun gene expression in response to TGF-β.
- Utilized human lung adenocarcinoma A549 cells, mouse embryo fibroblasts (AKR-2B), and K562 human erythroleukemia cells.
- Employed mRNA expression analysis, metabolic labeling, and immunoprecipitation.
Main Results:
- TGF-β rapidly increased junB and c-jun mRNA levels in a dose-dependent manner (picomolar concentrations).
- mRNA induction was followed by increased c-jun protein (AP-1) biosynthesis.
- Observed differential and cell-type-specific regulation of jun gene induction.
Conclusions:
- Early genomic response to TGF-β involves induction of junB and c-jun transcription factors.
- These transcription factors, along with c-fos, may mediate nuclear signal transduction and amplification.
- Differential jun gene activation could explain the pleiotropic effects of TGF-β.