Hippo Stabilises Its Adaptor Salvador by Antagonising the HECT Ubiquitin Ligase Herc4
| Autor: | Ieva Gailite, David Sims, Nicolas Tapon, Birgit L. Aerne |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Scaffold protein
HECT domain endocrine system Immunoprecipitation Ubiquitin-Protein Ligases Protein domain Molecular Sequence Data lcsh:Medicine Cell Cycle Proteins Protein Serine-Threonine Kinases Ubiquitin Animals Drosophila Proteins Amino Acid Sequence lcsh:Science Multidisciplinary biology lcsh:R fungi Intracellular Signaling Peptides and Proteins equipment and supplies Ubiquitin ligase body regions Biochemistry biology.protein Phosphorylation lcsh:Q Drosophila RNA Interference Signal transduction Protein Kinases Sequence Alignment Signal Transduction Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 6, p e0131113 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Signalling through the Hippo (Hpo) pathway involves a kinase cascade, which leads to the phosphorylation and inactivation of the pro-growth transcriptional co-activator Yorkie (Yki). Despite the identification of a large number of pathway members and modulators, our understanding of the molecular events that lead to activation of Hpo and the downstream kinase Warts (Wts) remain incomplete. Recently, targeted degradation of several Hpo pathway components has been demonstrated as a means of regulating pathway activity. In particular, the stability of scaffold protein Salvador (Sav), which is believed to promote Hpo/Wts association, is crucially dependent on its binding partner Hpo. In a cell-based RNAi screen for ubiquitin regulators involved in Sav stability, we identify the HECT domain protein Herc4 (HECT and RLD domain containing E3 ligase) as a Sav E3 ligase. Herc4 expression promotes Sav ubiquitylation and degradation, while Herc4 depletion stabilises Sav. Interestingly, Hpo reduces Sav/Herc4 interaction in a kinase-dependent manner. This suggests the existence of a positive feedback loop, where Hpo stabilises its own positive regulator by antagonising Herc4-mediated degradation of Sav. |
| Databáze: | OpenAIRE |
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