Abstract
c-Fos and c-Jun proteins are highly unstable transcription factors that heterodimerize within the AP-1 transcription complex. Their accumulation is transiently induced at the beginning of the G0-to-S phase transition in quiescent cells stimulated for growth. To address the mechanisms responsible for rapid clearance of c-Fos and c-Jun proteins under these experimental conditions, we have used the ts20 mouse embryo fibroblasts which express a thermosensitive mutant of the E1 enzyme of the ubiquitin pathway. The use of cell-permeant protease inhibitors indicates that both proteins are degraded by the proteasome and excludes any major contribution for calpains and lysosomes during the G0-to-S phase transition. Synchronisation of ts20 cells at the non permissive temperature blocks the degradation of c-Jun, indicating that this process is E1-dependent. In contrast, c-Fos is broken down according to an apparently E1-independent pathway in ts20 cells, although a role for ubiquitinylation in this process cannot be formally ruled out. Interestingly, c-Jun is highly unstable in c-Fos-null mouse embryo fibroblasts stimulated for growth. Taken together, these observations show that in vivo during a G0-to-S phase transition (i) the precise mechanisms triggering c-Fos and c-Jun directing to the proteasome are not identical, (ii) the presence of c-Fos is not an absolute prerequisite for the degradation of c-Jun and (iii) the degradation of c-Jun is not required for that of c-Fos.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Salvat, C., Jariel-Encontre, I., Acquaviva, C. et al. Differential directing of c-Fos and c-Jun proteins to the proteasome in serum-stimulated mouse embryo fibroblasts. Oncogene 17, 327–337 (1998). https://doi.org/10.1038/sj.onc.1201922
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201922
Keywords
This article is cited by
-
The structural determinants responsible for c-Fos protein proteasomal degradation differ according to the conditions of expression
Oncogene (2003)
-
Dual-specificity protein tyrosine phosphatase VHR down-regulates c-Jun N-terminal kinase (JNK)
Oncogene (2002)
-
Cellular and viral Fos proteins are degraded by different proteolytic systems
Oncogene (2001)
-
Identification of a C-terminal tripeptide motif involved in the control of rapid proteasomal degradation of c-Fos proto-oncoprotein during the G0-to-S phase transition
Oncogene (2001)