This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pertovaara, L Articles by Alitalo, K Search for Related Content PubMed PubMed Citation Articles by Pertovaara, L Articles by Alitalo, K

Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation.

Department 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.

This article has been cited by other articles:

• Zhu, Q., Krakowski, A. R., Dunham, E. E., Wang, L., Bandyopadhyay, A., Berdeaux, R., Martin, G. S., Sun, L., Luo, K. (2007). Dual Role of SnoN in Mammalian Tumorigenesis. Mol. Cell. Biol. 27: 324-339 [Abstract] [Full Text]  
• Matsuda, H., Fukuda, N., Ueno, T., Tahira, Y., Ayame, H., Zhang, W., Bando, T., Sugiyama, H., Saito, S., Matsumoto, K., Mugishima, H., Serie, K. (2006). Development of Gene Silencing Pyrrole-Imidazole Polyamide Targeting the TGF-beta1 Promoter for Treatment of Progressive Renal Diseases. J. Am. Soc. Nephrol. 17: 422-432 [Abstract] [Full Text]  
• Huang, C.-Y. C., Reuben, P. M., Cheung, H. S. (2005). Temporal Expression Patterns and Corresponding Protein Inductions of Early Responsive Genes in Rabbit Bone Marrow-Derived Mesenchymal Stem Cells Under Cyclic Compressive Loading. Stem Cells 23: 1113-1121 [Abstract] [Full Text]  
• Lee, M.-H., Kim, Y.-J., Kim, H.-J., Park, H.-D., Kang, A.-R., Kyung, H.-M., Sung, J.-H., Wozney, J. M., Kim, H.-J., Ryoo, H.-M. (2003). BMP-2-induced Runx2 Expression Is Mediated by Dlx5, and TGF-{beta}1 Opposes the BMP-2-induced Osteoblast Differentiation by Suppression of Dlx5 Expression. J. Biol. Chem. 278: 34387-34394 [Abstract] [Full Text]  
• Hulboy, D. L., Matrisian, L. M., Crawford, H. C. (2001). Loss of JunB Activity Enhances Stromelysin 1 Expression in a Model of the Epithelial-to-Mesenchymal Transition of Mouse Skin Tumors. Mol. Cell. Biol. 21: 5478-5487 [Abstract] [Full Text]  
• Chen, C.-R., Kang, Y., Massague, J. (2001). Inaugural Article: Defective repression of c-myc in breast cancer cells: A loss at the core of the transforming growth factor beta growth arrest program. Proc. Natl. Acad. Sci. USA 98: 992-999 [Abstract] [Full Text]  
• de Caestecker, M. P., Piek, E., Roberts, A. B. (2000). Role of Transforming Growth Factor-{beta} Signaling in Cancer. JNCI J Natl Cancer Inst 92: 1388-1402 [Abstract] [Full Text]  
• Cook, T., Urrutia, R. (2000). TIEG proteins join the Smads as TGF-beta -regulated transcription factors that control pancreatic cell growth. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G513-G521 [Abstract] [Full Text]  
• Kardassis, D., Papakosta, P., Pardali, K., Moustakas, A. (1999). c-Jun Transactivates the Promoter of the Human p21WAF1/Cip1 Gene by Acting as a Superactivator of the Ubiquitous Transcription Factor Sp1. J. Biol. Chem. 274: 29572-29581 [Abstract] [Full Text]  
• Hollnagel, A., Oehlmann, V., Heymer, J., Ruther, U., Nordheim, A. (1999). Id Genes Are Direct Targets of Bone Morphogenetic Protein Induction in Embryonic Stem Cells. J. Biol. Chem. 274: 19838-19845 [Abstract] [Full Text]  
• Cirillo, P., Golino, P., Ragni, M., Battaglia, C., Pacifico, F., Formisano, S., Buono, C., Condorelli, M., Chiariello, M. (1999). Activated platelets and leucocytes cooperatively stimulate smooth muscle cell proliferation and proto-oncogene expression via release of soluble growth factors. Cardiovasc Res 43: 210-218 [Abstract] [Full Text]  
• Liberati, N. T., Datto, M. B., Frederick, J. P., Shen, X., Wong, C., Rougier-Chapman, E. M., Wang, X.-F. (1999). Smads bind directly to the Jun family of AP-1 transcription factors. Proc. Natl. Acad. Sci. USA 96: 4844-4849 [Abstract] [Full Text]  
• Wong, C., Rougier-Chapman, E. M., Frederick, J. P., Datto, M. B., Liberati, N. T., Li, J.-M., Wang, X.-F. (1999). Smad3-Smad4 and AP-1 Complexes Synergize in Transcriptional Activation of the c-Jun Promoter by Transforming Growth Factor beta. Mol. Cell. Biol. 19: 1821-1830 [Abstract] [Full Text]  
• Zicha, D, Genot, E, Dunn, G., Kramer, I. (1999). TGFbeta1 induces a cell-cycle-dependent increase in motility of epithelial cells. J. Cell Sci. 112: 447-454 [Abstract]  
• Brand, C., Cherradi, N., Defaye, G., Chinn, A., Chambaz, E. M., Feige, J.-J., Bailly, S. (1998). Transforming Growth Factor beta 1 Decreases Cholesterol Supply to Mitochondria via Repression of Steroidogenic Acute Regulatory Protein Expression. J. Biol. Chem. 273: 6410-6416 [Abstract] [Full Text]  
• Chalaux, E., Lopez-Rovira, T., Rosa, J. L., Bartrons, R., Ventura, F. (1998). JunB Is Involved in the Inhibition of Myogenic Differentiation by Bone Morphogenetic Protein-2. J. Biol. Chem. 273: 537-543 [Abstract] [Full Text]  
• Döhr, O., Sinning, R., Vogel, C., Münzel, P., Abel, J. (1997). Effect of Transforming Growth Factor-beta 1 on Expression of Aryl Hydrocarbon Receptor and Genes of Ah Gene Battery: Clues for Independent Down-Regulation in A549 Cells. Mol. Pharmacol. 51: 703-710 [Abstract] [Full Text]  
• Mauviel, A., Chung, K.-Y., Agarwal, A., Tamai, K., Uitto, J. (1996). Cell-specific Induction of Distinct Oncogenes of the Jun Family Is Responsible for Differential Regulation of Collagenase Gene Expression by Transforming Growth Factor-beta in Fibroblasts and Keratinocytes. J. Biol. Chem. 271: 10917-10923 [Abstract] [Full Text]  
• Hartsough, M. T., Mulder, K. M. (1995). Transforming Growth Factor beta Activation of p44[IMAGE] in Proliferating Cultures of Epithelial Cells. J. Biol. Chem. 270: 7117-7124 [Abstract] [Full Text]  
• Chang, E., Goldberg, H. (1995). Requirements for Transforming Growth Factor-beta Regulation of the Pro-alpha2(I) Collagen and Plasminogen Activator Inhibitor-1 Promoters. J. Biol. Chem. 270: 4473-4477 [Abstract] [Full Text]  
• Treisman, J., Lai, Z., Rubin, G. (1995). Shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-beta-responsive gene. Development 121: 2835-2845 [Abstract]  
• Kramer, I., Patel, R, Spargo, D, Riley, P (1994). Initiation of growth inhibition by TGF beta 1 is unlikely to occur in G1. J. Cell Sci. 107: 3469-3475 [Abstract]  
• Deng, T, Karin, M (1993). JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers.. Genes Dev. 7: 479-490 [Abstract]  
• Bos, T J, Monteclaro, F S, Mitsunobu, F, Ball, A R, Chang, C H, Nishimura, T, Vogt, P K (1990). Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences.. Genes Dev. 4: 1677-1687 [Abstract]  
• Ney, P A, Sorrentino, B P, McDonagh, K T, Nienhuis, A W (1990). Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells.. Genes Dev. 4: 993-1006 [Abstract]  
• Muller, U, Roberts, M P, Engel, D A, Doerfler, W, Shenk, T (1989). Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP.. Genes Dev. 3: 1991-2002 [Abstract]  
• Shen, X., Li, J., Hu, P. P.-c., Waddell, D., Zhang, J., Wang, X.-F. (2001). The Activity of Guanine Exchange Factor NET1 Is Essential for Transforming Growth Factor-beta -mediated Stress Fiber Formation. J. Biol. Chem. 276: 15362-15368 [Abstract] [Full Text]