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p14ARF regulates E2F-1 ubiquitination and degradation via a p53-dependent mechanism.
- Source :
-
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2007 Jul 15; Vol. 6 (14), pp. 1741-7. Date of Electronic Publication: 2007 May 10. - Publication Year :
- 2007
-
Abstract
- Alterations in the ARF tumor suppressor protein (also known as p14ARF in humans and p19ARF in the mouse) occur frequently in cancer and are associated with susceptibility to melanoma, pancreatic cancer and nervous system tumors. ARF proteins interact with the E2F-1, -2 and -3 transcription activators to inhibit their transcriptional activity and induce their degradation via the 26S proteasome pathway. The impact of ARF on the E2F proteins may provide a mechanism for p53-independent ARF activity on cell cycle progression and tumor susceptibility. In this report we explored the effects of ARF on E2F ubiquitination and degradation in relationship to cell cycle effects and p53 status. We now show that ARF induced the rapid ubiquitination and degradation of E2F-1 only in the presence of functional p53. E2F-1 continued to be ubiquitinated following ARF induction in cycling p53-wild-type, p21-null cells, showing that effects of ARF were not simply a result of p14ARF induced cell-cycle arrest. Importantly, these data establish that the ARF-E2F-1 pathway is an extension of the p53-mdm2-ARF tumor suppressor network and is unlikely to constitute a p53-independent pathway for ARF function.
- Subjects :
- Animals
Cell Line, Tumor
E2F1 Transcription Factor genetics
Genetic Predisposition to Disease
Humans
Mice
Signal Transduction physiology
Tumor Suppressor Protein p14ARF genetics
Tumor Suppressor Protein p53 genetics
Ubiquitination
Cell Cycle physiology
E2F1 Transcription Factor metabolism
Tumor Suppressor Protein p14ARF metabolism
Tumor Suppressor Protein p53 metabolism
Ubiquitin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1551-4005
- Volume :
- 6
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Cell cycle (Georgetown, Tex.)
- Publication Type :
- Academic Journal
- Accession number :
- 17630509
- Full Text :
- https://doi.org/10.4161/cc.6.14.4428