| Added by | eric_julien |
|---|---|
| Group name | EquipeEJ |
| Item Type | Journal Article |
| Title | The stability of Fbw7? in M-phase requires its phosphorylation by PKC |
| Creator | Zitouni et al. |
| Author | Sihem Zitouni |
| Author | Catherine Papin |
| Author | Armelle Choquet |
| Author | Daniel Roche |
| Author | Véronique Baldin |
| Author | Olivier Coux |
| Author | Catherine Bonne-Andrea |
| Abstract | Fbw7 is a tumor suppressor often deleted or mutated in human cancers. It serves as the substrate-recruiting subunit of a SCF ubiquitin ligase that targets numerous critical proteins for degradation, including oncoproteins and master transcription factors. Cyclin E was the first identified substrate of the SCFFbw7 ubiquitin ligase. In human cancers bearing FBXW7-gene mutations, deregulation of cyclin E turnover leads to its aberrant expression in mitosis. We investigated Fbw7 regulation in Xenopus eggs, which, although arrested in a mitotic-like phase, naturally express high levels of cyclin E. Here, we report that Fbw7?, the only Fbw7 isoform detected in eggs, is phosphorylated by PKC (protein kinase C) at a key residue (S18) in a manner coincident with Fbw7? inactivation. We show that this PKC-dependent phosphorylation and inactivation of Fbw7? also occurs in mitosis during human somatic cell cycles, and importantly is critical for Fbw7? stabilization itself upon nuclear envelope breakdown. Finally, we provide evidence that S18 phosphorylation, which lies within the intrinsically disordered N-terminal region specific to the ?-isoform reduces the capacity of Fbw7? to dimerize and to bind cyclin E. Together, these findings implicate PKC in an evolutionarily-conserved pathway that aims to protect Fbw7? from degradation by keeping it transiently in a resting, inactive state. |
| Publication | PloS One |
| Volume | 12 |
| Issue | 8 |
| Pages | e0183500 |
| Date | 2017 |
| Journal Abbr | PLoS ONE |
| Language | eng |
| DOI | 10.1371/journal.pone.0183500 |
| ISSN | 1932-6203 |
| Library Catalog | PubMed |
| Extra | PMID: 28850619 PMCID: PMC5574586 |
| Tags | Animals, Cell Cycle Proteins, Cell Division, F-Box Proteins, F-Box-WD Repeat-Containing Protein 7, Humans, original, Phosphorylation, Protein Kinase C, Ubiquitin-Protein Ligases, Xenopus laevis |
| Date Added | 2019/05/28 - 13:51:42 |
| Date Modified | 2019/05/28 - 13:57:02 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
