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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.



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