This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burch, P. M.
Right arrow Articles by Heintz, N. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burch, P. M.
Right arrow Articles by Heintz, N. H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2004, p. 4696-4709, Vol. 24, No. 11
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.11.4696-4709.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

An Extracellular Signal-Regulated Kinase 1- and 2-Dependent Program of Chromatin Trafficking of c-Fos and Fra-1 Is Required for Cyclin D1 Expression during Cell Cycle Reentry

Peter M. Burch,1,2 Ziqiang Yuan,1 Anne Loonen,1 and Nicholas H. Heintz1,2*

Department of Pathology,1 Environmental Pathology Program, University of Vermont College of Medicine, Burlington, Vermont 054052

Received 5 January 2004/ Returned for modification 31 January 2004/ Accepted 4 March 2004

Mitogens activate cell signaling and gene expression cascades that culminate in expression of cyclin D1 during the G0-to-G1 transition of the cell cycle. Using cell cycle arrest in response to oxidative stress, we have delineated a dynamic program of chromatin trafficking of c-Fos and Fra-1 required for cyclin D1 expression during cell cycle reentry. In serum-stimulated lung epithelial cells, c-Fos was expressed, recruited to chromatin, phosphorylated at extracellular signal-regulated kinase 1- and 2 (ERK1,2)-dependent sites, and degraded prior to prolonged recruitment of Fra-1 to chromatin. Immunostaining showed that expression of nuclear c-Fos and that of cyclin D1 are mutually exclusive, whereas nuclear Fra-1 and cyclin D1 are coexpressed as cells traverse G1. Oxidative stress prolonged the accumulation of phospho-ERK1,2 and phospho-c-Fos on chromatin, inhibited entry of Fra-1 into the nucleus, and blocked cyclin D1 expression. After induction of the immediate-early gene response in the presence of oxidative stress, inhibition of ERK1,2 signaling promoted degradation of c-Fos, recruitment of Fra-1 to chromatin, and expression of cyclin D1. Our data indicate that termination of nuclear ERK1,2 signaling is required for an exchange of Fra-1 for c-Fos on chromatin and initiation of cyclin D1 expression at the G0-to-G1 transition of the cell cycle.

* Corresponding author. Mailing address: Department of Pathology, Vermont Cancer Center, HSRF 328, University of Vermont College of Medicine, 89 Beaumont Ave., Burlington, VT 05405. Phone: (802) 656-0372. Fax: (802) 656-8892. E-mail: Nicholas.Heintz{at}uvm.edu.

Molecular and Cellular Biology, June 2004, p. 4696-4709, Vol. 24, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.11.4696-4709.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Geest, C. R., Buitenhuis, M., Groot Koerkamp, M. J. A., Holstege, F. C. P., Vellenga, E., Coffer, P. J. (2009). Tight control of MEK-ERK activation is essential in regulating proliferation, survival, and cytokine production of CD34+-derived neutrophil progenitors. Blood 114: 3402-3412 [Abstract] [Full Text]  
  • Klein, E. A., Assoian, R. K. (2008). Transcriptional regulation of the cyclin D1 gene at a glance. J. Cell Sci. 121: 3853-3857 [Full Text]  
  • Ramos-Nino, M. E., Blumen, S. R., Sabo-Attwood, T., Pass, H., Carbone, M., Testa, J. R., Altomare, D. A., Mossman, B. T. (2008). HGF Mediates Cell Proliferation of Human Mesothelioma Cells through a PI3K/MEK5/Fra-1 Pathway. Am. J. Respir. Cell Mol. Bio. 38: 209-217 [Abstract] [Full Text]  
  • Glauser, D. A., Schlegel, W. (2007). Sequential actions of ERK1/2 on the AP-1 transcription factor allow temporal integration of metabolic signals in pancreatic {beta} cells. FASEB J. 21: 3240-3249 [Abstract] [Full Text]  
  • Cho, H.-J., Kang, J. H., Kwak, J.-Y., Lee, T.-S., Lee, I.-S., Park, N. G., Nakajima, H., Magae, J., Chang, Y.-C. (2007). Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK- and Ap1-dependent mechanisms. Carcinogenesis 28: 1104-1110 [Abstract] [Full Text]  
  • Phalen, T. J., Weirather, K., Deming, P. B., Anathy, V., Howe, A. K., van der Vliet, A., Jonsson, T. J., Poole, L. B., Heintz, N. H. (2006). Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery. JCB 175: 779-789 [Abstract] [Full Text]  
  • Hyun, J., Becam, I., Yanicostas, C., Bohmann, D. (2006). Control of G2/M Transition by Drosophila Fos. Mol. Cell. Biol. 26: 8293-8302 [Abstract] [Full Text]  
  • Shukla, A., Barrett, T. F., Nakayama, K. I., Nakayama, K., Mossman, B. T., Lounsbury, K. M. (2006). Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKC{delta}-dependent pathway in murine lung. FASEB J. 20: 997-999 [Abstract] [Full Text]  
  • Kakumoto, K., Sasai, K., Sukezane, T., Oneyama, C., Ishimaru, S., Shibutani, K., Mizushima, H., Mekada, E., Hanafusa, H., Akagi, T. (2006). FRA1 is a determinant for the difference in RAS-induced transformation between human and rat fibroblasts. Proc. Natl. Acad. Sci. USA 103: 5490-5495 [Abstract] [Full Text]  
  • Barlow, C. A., Shukla, A., Mossman, B. T., Lounsbury, K. M. (2006). Oxidant-Mediated cAMP Response Element Binding Protein Activation: Calcium Regulation and Role in Apoptosis of Lung Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 34: 7-14 [Abstract] [Full Text]  
  • Haegens, A., van der Vliet, A., Butnor, K. J., Heintz, N., Taatjes, D., Hemenway, D., Vacek, P., Freeman, B. A., Hazen, S. L., Brennan, M. L., Mossman, B. T. (2005). Asbestos-Induced Lung Inflammation and Epithelial Cell Proliferation Are Altered in Myeloperoxidase-Null Mice. Cancer Res. 65: 9670-9677 [Abstract] [Full Text]  
  • Hong, S., Park, K.-K., Magae, J., Ando, K., Lee, T.-S., Kwon, T. K., Kwak, J.-Y., Kim, C.-H., Chang, Y.-C. (2005). Ascochlorin Inhibits Matrix Metalloproteinase-9 Expression by Suppressing Activator Protein-1-mediated Gene Expression through the ERK1/2 Signaling Pathway: INHIBITORY EFFECTS OF ASCOCHLORIN ON THE INVASION OF RENAL CARCINOMA CELLS. J. Biol. Chem. 280: 25202-25209 [Abstract] [Full Text]  
  • Yan, J., Hales, B. F. (2005). Activator Protein-1 (AP-1) DNA Binding Activity Is Induced by Hydroxyurea in Organogenesis Stage Mouse Embryos. Toxicol Sci 85: 1013-1023 [Abstract] [Full Text]  
  • Yuan, Z., Taatjes, D. J., Mossman, B. T., Heintz, N. H. (2004). The Duration of Nuclear Extracellular Signal-Regulated Kinase 1 and 2 Signaling during Cell Cycle Reentry Distinguishes Proliferation from Apoptosis in Response to Asbestos. Cancer Res. 64: 6530-6536 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»