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 Bossis, G.
Right arrow Articles by Piechaczyk, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bossis, G.
Right arrow Articles by Piechaczyk, M.

 Previous Article

Molecular and Cellular Biology, October 2003, p. 7425-7436, Vol. 23, No. 20
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.20.7425-7436.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

c-Fos Proto-Oncoprotein Is Degraded by the Proteasome Independently of Its Own Ubiquitinylation In Vivo

Guillaume Bossis, Patrizia Ferrara, Claire Acquaviva, Isabelle Jariel-Encontre, and Marc Piechaczyk*

Institute of Molecular Genetics, UMR5535/IFR122, CNRS, 34293 Montpellier Cédex 05, France

Received 17 March 2003/ Returned for modification 17 June 2003/ Accepted 17 July 2003

Prior ubiquitinylation of the unstable c-Fos proto-oncoprotein is thought to be required for recognition and degradation by the proteasome. Contradicting this view, we report that, although c-Fos can form conjugates with ubiquitin in vivo, nonubiquitinylatable c-Fos mutants show regulated degradation identical to that of the wild-type protein in living cells under two classical conditions of study: transient c-fos gene expression during the G0/G1 phase transition upon stimulation by mitogens and constitutive expression during asynchronous growth. Moreover, c-Fos destruction during the G0/G1 phase transition is unusual because it depends on two distinct but cumulative mechanisms. We report here that one mechanism involves a C-terminal destabilizer which does not need an active ubiquitin cycle, whereas the other involves an N-terminal destabilizer dependent on ubiquitinylation of an upstream c-Fos breakdown effector. In addition to providing new insights into the mechanisms of c-Fos protein destruction, an important consequence of our work is that ubiquitinylation-dependent proteasomal degradation claimed for a number of proteins should be reassessed on a new experimental basis.

* Corresponding author. Mailing address: Institute of Molecular Genetics, UMR5535/IFR122, CNRS, 1919, route de Mende, 34293 Montpellier Cédex 05, France. Phone: 33 4 67 61 36 68. Fax: 33 4 67 04 02 31. E-mail: piechaczyk{at}igm.cnrs-mop.fr.

Molecular and Cellular Biology, October 2003, p. 7425-7436, Vol. 23, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.20.7425-7436.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gonzalez, J. M., Navarro-Puche, A., Casar, B., Crespo, P., Andres, V. (2008). Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. JCB 183: 653-666 [Abstract] [Full Text]  
  • Farras, R., Baldin, V., Gallach, S., Acquaviva, C., Bossis, G., Jariel-Encontre, I., Piechaczyk, M. (2008). JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis. Mol. Cell. Biol. 28: 4173-4187 [Abstract] [Full Text]  
  • Malnou, C. E., Salem, T., Brockly, F., Wodrich, H., Piechaczyk, M., Jariel-Encontre, I. (2007). Heterodimerization with Jun Family Members Regulates c-Fos Nucleocytoplasmic Traffic. J. Biol. Chem. 282: 31046-31059 [Abstract] [Full Text]  
  • Basbous, J., Chalbos, D., Hipskind, R., Jariel-Encontre, I., Piechaczyk, M. (2007). Ubiquitin-Independent Proteasomal Degradation of Fra-1 Is Antagonized by Erk1/2 Pathway-Mediated Phosphorylation of a Unique C-Terminal Destabilizer. Mol. Cell. Biol. 27: 3936-3950 [Abstract] [Full Text]  
  • Kuballa, P., Matentzoglu, K., Scheffner, M. (2007). The Role of the Ubiquitin Ligase E6-AP in Human Papillomavirus E6-mediated Degradation of PDZ Domain-containing Proteins. J. Biol. Chem. 282: 65-71 [Abstract] [Full Text]  
  • Relic, B., Benoit, V., Franchimont, N., Kaiser, M.-J., Hauzeur, J.-P., Gillet, P., Merville, M.-P., Bours, V., Malaise, M. G. (2006). Peroxisome Proliferator-activated Receptor-{gamma}1 Is Dephosphorylated and Degraded during BAY 11-7085-induced Synovial Fibroblast Apoptosis. J. Biol. Chem. 281: 22597-22604 [Abstract] [Full Text]  
  • Bossis, G., Malnou, C. E., Farras, R., Andermarcher, E., Hipskind, R., Rodriguez, M., Schmidt, D., Muller, S., Jariel-Encontre, I., Piechaczyk, M. (2005). Down-Regulation of c-Fos/c-Jun AP-1 Dimer Activity by Sumoylation. Mol. Cell. Biol. 25: 6964-6979 [Abstract] [Full Text]  
  • Krummel, K. A., Lee, C. J., Toledo, F., Wahl, G. M. (2005). The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation. Proc. Natl. Acad. Sci. USA 102: 10188-10193 [Abstract] [Full Text]  
  • Biggs, J. R., Zhang, Y., Peterson, L. F., Garcia, M., Zhang, D.-E., Kraft, A. S. (2005). Phosphorylation of AML1/RUNX1 Regulates Its Degradation and Nuclear Matrix Association. Mol Cancer Res 3: 391-401 [Abstract] [Full Text]  
  • Hipp, M. S., Kalveram, B., Raasi, S., Groettrup, M., Schmidtke, G. (2005). FAT10, a Ubiquitin-Independent Signal for Proteasomal Degradation. Mol. Cell. Biol. 25: 3483-3491 [Abstract] [Full Text]  
  • Hoffmann, E., Thiefes, A., Buhrow, D., Dittrich-Breiholz, O., Schneider, H., Resch, K., Kracht, M. (2005). MEK1-dependent Delayed Expression of Fos-related Antigen-1 Counteracts c-Fos and p65 NF-{kappa}B-mediated Interleukin-8 Transcription in Response to Cytokines or Growth Factors. J. Biol. Chem. 280: 9706-9718 [Abstract] [Full Text]  
  • Ju, D., Xie, Y. (2004). Proteasomal Degradation of RPN4 via Two Distinct Mechanisms, Ubiquitin-dependent and -independent. J. Biol. Chem. 279: 23851-23854 [Abstract] [Full Text]  
  • Yerlikaya, A., Stanley, B. A. (2004). S-Adenosylmethionine Decarboxylase Degradation by the 26 S Proteasome Is Accelerated by Substrate-mediated Transamination. J. Biol. Chem. 279: 12469-12478 [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»