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Isoform- and cell cycle–dependent substrate degradation by the Fbw7 ubiquitin ligase
| Content Provider | Scilit |
|---|---|
| Author | Grim, Jonathan E. Gustafson, Michael P. Hirata, Roli K. Hagar, Amanda C. Swanger, Jherek Welcker, Markus Hwang, Harry C. Ericsson, Johan Russell, David W. Clurman, Bruce E. |
| Copyright Year | 2008 |
| Description | The SCFFBW7 ubiquitin ligase degrades proteins involved in cell division, growth, and differentiation and is commonly mutated in cancers. The Fbw7 locus encodes three protein isoforms that occupy distinct subcellular localizations, suggesting that each has unique functions. We used gene targeting to create isoform-specific Fbw7-null mutations in human cells and found that the nucleoplasmic Fbw7α isoform accounts for almost all Fbw7 activity toward cyclin E, c-Myc, and sterol regulatory element binding protein 1. Cyclin E sensitivity to Fbw7 varies during the cell cycle, and this correlates with changes in cyclin E–cyclin-dependent kinase 2 (CDK2)–specific activity, cyclin E autophosphorylation, and CDK2 inhibitory phosphorylation. These data suggest that oscillations in cyclin E–CDK2-specific activity during the cell cycle regulate the timing of cyclin E degradation. Moreover, they highlight the utility of adeno-associated virus–mediated gene targeting in functional analyses of complex loci. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2426948/pdf |
| Ending Page | 920 |
| Page Count | 8 |
| Starting Page | 913 |
| DOI | 10.1083/jcb.200802076 |
| Journal | Journal of Cell Biology |
| Issue Number | 6 |
| Volume Number | 181 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2008-06-16 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Differentiation Protein Phosphorylation Functional Cell Cycle Fbw7 Ubiquitin Ligase Cdk2 Isoform Journal: Journal of Cell Biology (Vol- 181, Issue- 6) |
| Content Type | Text |
